rs251177

Variant names:

• chr5-141647317-T-C
• rs251177
• NM_033449.3:c.828+81A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033449.3(FCHSD1):​c.828+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,561,704 control chromosomes in the GnomAD database, including 41,789 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 0.25 (5430 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36359 hom.)
• Consequence: FCHSD1 NM_033449.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 18 publications found

Genes affected

FCHSD1 (HGNC:25463): (FCH and double SH3 domains 1) Predicted to enable lipid binding activity. Predicted to be involved in neuromuscular synaptic transmission and positive regulation of actin filament polymerization. Predicted to be located in cell projection and perikaryon. Predicted to be active in neuromuscular junction and recycling endosome. Predicted to colocalize with cuticular plate. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHSD1	NM_033449.3	c.828+81A>G		intron_variant	Intron 9 of 19	ENST00000435817.7	NP_258260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCHSD1	ENST00000435817.7	c.828+81A>G		intron_variant	Intron 9 of 19	1	NM_033449.3	ENSP00000399259.2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38417 AN: 151916 Hom.: 5431 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.00947

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.222 AC: 312635 AN: 1409670 Hom.: 36359 Cov.: 32 AF XY: 0.220 AC XY: 153113 AN XY: 695422

African (AFR) AF: 0.365 AC: 11643 AN: 31928

American (AMR) AF: 0.144 AC: 5397 AN: 37404

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7114 AN: 24382

East Asian (EAS) AF: 0.00535 AC: 203 AN: 37952

South Asian (SAS) AF: 0.150 AC: 12078 AN: 80616

European-Finnish (FIN) AF: 0.183 AC: 9374 AN: 51298

Middle Eastern (MID) AF: 0.301 AC: 1565 AN: 5196

European-Non Finnish (NFE) AF: 0.233 AC: 252117 AN: 1082668

Other (OTH) AF: 0.226 AC: 13144 AN: 58226

GnomAD4 genome AF: 0.253 AC: 38435 AN: 152034 Hom.: 5430 Cov.: 32 AF XY: 0.246 AC XY: 18283 AN XY: 74308

African (AFR) AF: 0.359 AC: 14883 AN: 41450

American (AMR) AF: 0.207 AC: 3158 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3468

East Asian (EAS) AF: 0.00949 AC: 49 AN: 5164

South Asian (SAS) AF: 0.140 AC: 673 AN: 4820

European-Finnish (FIN) AF: 0.182 AC: 1919 AN: 10564

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15917 AN: 67964

Other (OTH) AF: 0.246 AC: 520 AN: 2110

Alfa AF: 0.241 Hom.: 7997

Bravo AF: 0.261

Asia WGS AF: 0.0930 AC: 324 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.75
PhyloP100		-1.2
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: rs251177; hg19: chr5-141026884; COSMIC: COSV71302311; COSMIC: COSV71302311;