5-141647317-T-C

Position:

• chr5-141647317-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

FCHSD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FCHSD1	NM_033449.3	c.828+81A>G		intron_variant		ENST00000435817.7	NP_258260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCHSD1	ENST00000435817.7	c.828+81A>G		intron_variant		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

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.00535

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.226

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

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.00949

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.246

Alfa AF: 0.237 Hom.: 6108

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

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: rs251177; hg19: chr5-141026884; COSMIC: COSV71302311; COSMIC: COSV71302311;