19-17762764-C-T

Position:

• chr19-17762764-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2 BP4_Strong BP6_Moderate BP7 BS1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: FCHO1 NM_015122.3 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.51

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCHO1	NM_015122.3	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29	ENST00000596536.6	NP_055937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCHO1	ENST00000699203.1	c.-121C>T		splice_region_variant	3/22			ENSP00000514201.1
FCHO1	ENST00000596536.6	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29	5	NM_015122.3	ENSP00000470731.1
FCHO1	ENST00000699212.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/30			ENSP00000514208.1
FCHO1	ENST00000594202.6	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29	5		ENSP00000473001.1
FCHO1	ENST00000596309.6	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29	4		ENSP00000470511.2
FCHO1	ENST00000596951.6	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29	5		ENSP00000472417.1
FCHO1	ENST00000600209.6	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29	5		ENSP00000469075.2
FCHO1	ENST00000600676.5	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	4/28	2		ENSP00000470493.1
FCHO1	ENST00000699176.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29			ENSP00000514179.1
FCHO1	ENST00000699177.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29			ENSP00000514180.1
FCHO1	ENST00000699207.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29			ENSP00000514204.1
FCHO1	ENST00000699209.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29			ENSP00000514206.1
FCHO1	ENST00000699215.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	4/28			ENSP00000514211.1
FCHO1	ENST00000699202.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29			ENSP00000514200.1
FCHO1	ENST00000699214.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	4/28			ENSP00000514210.1
FCHO1	ENST00000699208.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/28			ENSP00000514205.1
FCHO1	ENST00000699198.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/29			ENSP00000514196.1
FCHO1	ENST00000699199.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	4/28			ENSP00000514197.1
FCHO1	ENST00000699213.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	4/28			ENSP00000514209.1
FCHO1	ENST00000699197.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/28			ENSP00000514195.1
FCHO1	ENST00000699200.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/28			ENSP00000514198.1
FCHO1	ENST00000699196.1	c.30C>T	p.Gly10Gly	splice_region_variant, synonymous_variant	5/27			ENSP00000514194.1
FCHO1	ENST00000699203	c.-121C>T		5_prime_UTR_variant	3/22			ENSP00000514201.1
FCHO1	ENST00000699201.1	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	5/28			ENSP00000514199.1
FCHO1	ENST00000699205.1	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	5/27			ENSP00000514202.1
FCHO1	ENST00000699206.1	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	5/29			ENSP00000514203.1
FCHO1	ENST00000699210.1	n.30C>T		splice_region_variant, non_coding_transcript_exon_variant	5/28			ENSP00000514207.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152102 Hom.: 0 Cov.: 31

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

GnomAD3 exomes AF: 0.0000318 AC: 8 AN: 251454 Hom.: 0 AF XY: 0.0000294 AC XY: 4 AN XY: 135896

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 SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1459472 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 726290

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152220 Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11 AN XY: 74426

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.5
DANN	Benign	0.87
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

LitVar

Other links and lift over

dbSNP: rs181173877; hg19: chr19-17873573;