19-17755200-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015122.3(FCHO1):c.27+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,605,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FCHO1
NM_015122.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-17755200-C-T is Benign according to our data. Variant chr19-17755200-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1569195.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHO1	NM_015122.3 link	c.27+9C>T		intron_variant	Intron 4 of 28	ENST00000596536.6	NP_055937.1	O14526-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCHO1	ENST00000596536.6 link	c.27+9C>T	intron_variant	Intron 4 of 28	5	NM_015122.3	ENSP00000470731.1	O14526-1
FCHO1	ENST00000699212.1 link	c.27+9C>T	intron_variant	Intron 4 of 29			ENSP00000514208.1	A0A8V8TPN1
FCHO1	ENST00000594202.6 link	c.27+9C>T	intron_variant	Intron 4 of 28	5		ENSP00000473001.1	A0A0C3SFZ9
FCHO1	ENST00000596309.6 link	c.27+9C>T	intron_variant	Intron 4 of 28	4		ENSP00000470511.2	O14526-1M0QZF0
FCHO1	ENST00000596951.6 link	c.27+9C>T	intron_variant	Intron 4 of 28	5		ENSP00000472417.1	O14526-1
FCHO1	ENST00000600209.6 link	c.27+9C>T	intron_variant	Intron 4 of 28	5		ENSP00000469075.2	O14526-1M0QXD1
FCHO1	ENST00000600676.5 link	c.27+9C>T	intron_variant	Intron 3 of 27	2		ENSP00000470493.1	O14526-1
FCHO1	ENST00000699176.1 link	c.27+9C>T	intron_variant	Intron 4 of 28			ENSP00000514179.1	O14526-1
FCHO1	ENST00000699177.1 link	c.27+9C>T	intron_variant	Intron 4 of 28			ENSP00000514180.1	O14526-1
FCHO1	ENST00000699207.1 link	c.27+9C>T	intron_variant	Intron 4 of 28			ENSP00000514204.1	O14526-1
FCHO1	ENST00000699209.1 link	c.27+9C>T	intron_variant	Intron 4 of 28			ENSP00000514206.1	O14526-1
FCHO1	ENST00000699215.1 link	c.27+9C>T	intron_variant	Intron 3 of 27			ENSP00000514211.1	O14526-1
FCHO1	ENST00000699202.1 link	c.27+9C>T	intron_variant	Intron 4 of 28			ENSP00000514200.1	A0A8V8TMX9
FCHO1	ENST00000699214.1 link	c.27+9C>T	intron_variant	Intron 3 of 27			ENSP00000514210.1	A0A8V8TMX9
FCHO1	ENST00000699208.1 link	c.27+9C>T	intron_variant	Intron 4 of 27			ENSP00000514205.1	A0A8V8TPA0
FCHO1	ENST00000699198.1 link	c.27+9C>T	intron_variant	Intron 4 of 28			ENSP00000514196.1	M0QYA9
FCHO1	ENST00000699199.1 link	c.27+9C>T	intron_variant	Intron 3 of 27			ENSP00000514197.1	M0QYA9
FCHO1	ENST00000699213.1 link	c.27+9C>T	intron_variant	Intron 3 of 27			ENSP00000514209.1	M0QYA9
FCHO1	ENST00000699197.1 link	c.27+9C>T	intron_variant	Intron 4 of 27			ENSP00000514195.1	A0A8V8TNC3
FCHO1	ENST00000699200.1 link	c.27+9C>T	intron_variant	Intron 4 of 27			ENSP00000514198.1	A0A8V8TNC3
FCHO1	ENST00000699196.1 link	c.27+9C>T	intron_variant	Intron 4 of 26			ENSP00000514194.1	A0A8V8TP91
FCHO1	ENST00000699203.1 link	c.-124+734C>T	intron_variant	Intron 2 of 21			ENSP00000514201.1	A0A8V8TPM7
FCHO1	ENST00000699201.1 link	n.27+9C>T	intron_variant	Intron 4 of 27			ENSP00000514199.1	A0A8V8TP96
FCHO1	ENST00000699205.1 link	n.27+9C>T	intron_variant	Intron 4 of 26			ENSP00000514202.1	A0A8V8TMV7
FCHO1	ENST00000699206.1 link	n.27+9C>T	intron_variant	Intron 4 of 28			ENSP00000514203.1	A0A8V8TMV7
FCHO1	ENST00000699210.1 link	n.27+9C>T	intron_variant	Intron 4 of 27			ENSP00000514207.1	A0A8V8TND1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000410

AC:

AN:

243738

AF XY:

0.00000758

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453730

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722802

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33122

American (AMR)

AF:

0.00

AC:

AN:

43334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25642

East Asian (EAS)

AF:

0.00

AC:

AN:

39374

South Asian (SAS)

AF:

0.00

AC:

AN:

85496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107740

Other (OTH)

AF:

0.00

AC:

AN:

60046

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41528

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 19, 2022

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

-0.88

CADD

Benign

0.022

(source)

DANN

Benign

0.84

PhyloP100

-1.6

PromoterAI

-0.015

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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19-17755200-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over