19-17769819-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015122.3(FCHO1):c.337-606T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,944 control chromosomes in the GnomAD database, including 16,168 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16168 hom., cov: 33)
• Consequence: FCHO1 NM_015122.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCHO1	NM_015122.3	c.337-606T>G		intron_variant		ENST00000596536.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCHO1	ENST00000596536.6	c.337-606T>G		intron_variant		5	NM_015122.3	P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68167 AN: 151826 Hom.: 16136 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68248 AN: 151944 Hom.: 16168 Cov.: 33 AF XY: 0.450 AC XY: 33446 AN XY: 74260

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.481

Alfa AF: 0.397 Hom.: 24752

Bravo AF: 0.474

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.9
Dann	Benign	0.70

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: rs4808095; hg19: chr19-17880628;