rs593753

Variant names:

• chr11-72980395-T-C
• rs593753
• NM_014824.3:c.705+3693A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014824.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHSD2	NM_014824.3	MANE Select	c.705+3693A>G		intron	N/A	NP_055639.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHSD2	ENST00000409418.9	TSL:2 MANE Select	c.705+3693A>G		intron	N/A	ENSP00000386722.4
	FCHSD2	ENST00000311172.11	TSL:1	c.537+3693A>G		intron	N/A	ENSP00000308978.7
	FCHSD2	ENST00000409853.5	TSL:1	c.537+3693A>G		intron	N/A	ENSP00000386314.1

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

African (AFR) AF: 0.871 AC: 36138 AN: 41470

American (AMR) AF: 0.755 AC: 11501 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2678 AN: 3468

East Asian (EAS) AF: 0.697 AC: 3601 AN: 5170

South Asian (SAS) AF: 0.866 AC: 4169 AN: 4816

European-Finnish (FIN) AF: 0.854 AC: 9027 AN: 10576

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51952 AN: 67962

Other (OTH) AF: 0.765 AC: 1610 AN: 2104

Alfa AF: 0.776 Hom.: 32972

Bravo AF: 0.787

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.016
DANN	Benign	0.38
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs593753; hg19: chr11-72691440;