rs593753

chr11-72980395-T-C

Variant summary

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

The NM_014824.3(FCHSD2):c.705+3693A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,012 control chromosomes in the GnomAD database, including 48,822 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 0.80 (48822 hom., cov: 30)
• Consequence: FCHSD2 NM_014824.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

Genes affected

FCHSD2 (HGNC:29114): (FCH and double SH3 domains 2) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in clathrin-dependent endocytosis and positive regulation of Arp2/3 complex-mediated actin nucleation. Located in plasma membrane. Colocalizes with clathrin-coated pit. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCHSD2	NM_014824.3	c.705+3693A>G		intron_variant		ENST00000409418.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCHSD2	ENST00000409418.9	c.705+3693A>G		intron_variant		2	NM_014824.3	P1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121422 AN: 151894 Hom.: 48766 Cov.: 30

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.799 AC: 121533 AN: 152012 Hom.: 48822 Cov.: 30 AF XY: 0.804 AC XY: 59725 AN XY: 74306

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.765

Alfa AF: 0.779 Hom.: 23055

Bravo AF: 0.787

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.016
Dann	Benign	0.38

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: rs593753; hg19: chr11-72691440;