19-17762764-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_015122.3(FCHO1):c.30C>T(p.Gly10Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,611,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G10G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FCHO1
NM_015122.3 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.51

Publications

0 publications found

Variant links:

Genes affected

FCHO1 (HGNC:29002): (FCH and mu domain containing endocytic adaptor 1) Enables AP-2 adaptor complex binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in cytosol; nucleoplasm; and plasma membrane. Is active in clathrin-coated pit. Implicated in primary immunodeficiency disease. [provided by Alliance of Genome Resources, Apr 2022]

FCHO1 Gene-Disease associations (from GenCC):

immunodeficiency 76
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

FCHO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-17762764-C-T is Benign according to our data. Variant chr19-17762764-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1520124.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000985 (15/152220) while in subpopulation AFR AF = 0.000337 (14/41528). AF 95% confidence interval is 0.000204. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHO1	NM_015122.3 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29	ENST00000596536.6	NP_055937.1	O14526-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCHO1	ENST00000699203.1 link	c.-121C>T		splice_region_variant	Exon 3 of 22			ENSP00000514201.1	A0A8V8TPM7
FCHO1	ENST00000596536.6 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29	5	NM_015122.3	ENSP00000470731.1	O14526-1
FCHO1	ENST00000699212.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 30			ENSP00000514208.1	A0A8V8TPN1
FCHO1	ENST00000594202.6 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29	5		ENSP00000473001.1	A0A0C3SFZ9
FCHO1	ENST00000596309.6 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29	4		ENSP00000470511.2	O14526-1M0QZF0
FCHO1	ENST00000596951.6 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29	5		ENSP00000472417.1	O14526-1
FCHO1	ENST00000600209.6 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29	5		ENSP00000469075.2	O14526-1M0QXD1
FCHO1	ENST00000600676.5 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 4 of 28	2		ENSP00000470493.1	O14526-1
FCHO1	ENST00000699176.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29			ENSP00000514179.1	O14526-1
FCHO1	ENST00000699177.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29			ENSP00000514180.1	O14526-1
FCHO1	ENST00000699207.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29			ENSP00000514204.1	O14526-1
FCHO1	ENST00000699209.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29			ENSP00000514206.1	O14526-1
FCHO1	ENST00000699215.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 4 of 28			ENSP00000514211.1	O14526-1
FCHO1	ENST00000699202.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29			ENSP00000514200.1	A0A8V8TMX9
FCHO1	ENST00000699214.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 4 of 28			ENSP00000514210.1	A0A8V8TMX9
FCHO1	ENST00000699208.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 28			ENSP00000514205.1	A0A8V8TPA0
FCHO1	ENST00000699198.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 29			ENSP00000514196.1	M0QYA9
FCHO1	ENST00000699199.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 4 of 28			ENSP00000514197.1	M0QYA9
FCHO1	ENST00000699213.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 4 of 28			ENSP00000514209.1	M0QYA9
FCHO1	ENST00000699197.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 28			ENSP00000514195.1	A0A8V8TNC3
FCHO1	ENST00000699200.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 28			ENSP00000514198.1	A0A8V8TNC3
FCHO1	ENST00000699196.1 link	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	Exon 5 of 27			ENSP00000514194.1	A0A8V8TP91
FCHO1	ENST00000699201.1 link	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 28			ENSP00000514199.1	A0A8V8TP96
FCHO1	ENST00000699205.1 link	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 27			ENSP00000514202.1	A0A8V8TMV7
FCHO1	ENST00000699206.1 link	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 29			ENSP00000514203.1	A0A8V8TMV7
FCHO1	ENST00000699210.1 link	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 28			ENSP00000514207.1	A0A8V8TND1
FCHO1	ENST00000699203.1 link	c.-121C>T		5_prime_UTR_variant	Exon 3 of 22			ENSP00000514201.1	A0A8V8TPM7

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000318

AC:

AN:

251454

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1459472

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726290

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109794

Other (OTH)

AF:

0.0000332

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41528

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.564

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.5

(source)

DANN

Benign

0.87

PhyloP100

-2.5

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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19-17762764-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over