19-17762730-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015122.3(FCHO1):c.28-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,503,916 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (38 hom.)
• Consequence: FCHO1 NM_015122.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.140

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048695803).
• BP6: Variant 19-17762730-C-T is Benign according to our data. Variant chr19-17762730-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00317 (483/152280) while in subpopulation NFE AF= 0.00545 (371/68026). AF 95% confidence interval is 0.005. There are 1 homozygotes in gnomad4. There are 214 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCHO1	NM_015122.3	c.28-32C>T		intron_variant		ENST00000596536.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCHO1	ENST00000596536.6	c.28-32C>T		intron_variant		5	NM_015122.3	P1

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 483 AN: 152162 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00545

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00354 AC: 891 AN: 251360 Hom.: 6 AF XY: 0.00379 AC XY: 515 AN XY: 135848

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00369

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00546

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00574 AC: 7758 AN: 1351636 Hom.: 38 Cov.: 22 AF XY: 0.00578 AC XY: 3926 AN XY: 678988

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00211

Gnomad4 ASJ exome AF: 0.00400

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00350

Gnomad4 FIN exome AF: 0.000487

Gnomad4 NFE exome AF: 0.00679

Gnomad4 OTH exome AF: 0.00566

GnomAD4 genome AF: 0.00317 AC: 483 AN: 152280 Hom.: 1 Cov.: 31 AF XY: 0.00287 AC XY: 214 AN XY: 74450

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.00236

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00545

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00437 Hom.: 0

Bravo AF: 0.00361

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00581 AC: 50

ExAC AF: 0.00355 AC: 431

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00725

EpiControl AF: 0.00658

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

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

FCHO1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	0.90
Dann	Benign	0.79
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.0049	T
MutationTaster	Benign	1.0	N;N;N
Sift4G	Benign	0.44	T
Vest4		0.13
MVP		0.35
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

LitVar

Other links and lift over

dbSNP: rs117245024; hg19: chr19-17873539;