rs456998

Variant names:

• chr5-141645595-G-T
• rs456998
• NM_033449.3:c.1311+176C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-141645595-G-T
• chr5-141645595-G-C

Variant summary

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

The NM_033449.3(FCHSD1):​c.1311+176C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,094 control chromosomes in the GnomAD database, including 25,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.57 (25518 hom., cov: 33)
• Consequence: FCHSD1 NM_033449.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 17 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033449.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHSD1	NM_033449.3	MANE Select	c.1311+176C>A		intron	N/A	NP_258260.1	Q86WN1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHSD1	ENST00000435817.7	TSL:1 MANE Select	c.1311+176C>A		intron	N/A	ENSP00000399259.2	Q86WN1-1
	FCHSD1	ENST00000896539.1		c.1419+176C>A		intron	N/A	ENSP00000566598.1
	FCHSD1	ENST00000896537.1		c.1305+176C>A		intron	N/A	ENSP00000566596.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86121 AN: 151976 Hom.: 25485 Cov.: 33

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.567 AC: 86212 AN: 152094 Hom.: 25518 Cov.: 33 AF XY: 0.562 AC XY: 41779 AN XY: 74358

African (AFR) AF: 0.743 AC: 30840 AN: 41494

American (AMR) AF: 0.582 AC: 8890 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1257 AN: 5172

South Asian (SAS) AF: 0.438 AC: 2110 AN: 4818

European-Finnish (FIN) AF: 0.492 AC: 5197 AN: 10572

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34594 AN: 67964

Other (OTH) AF: 0.548 AC: 1156 AN: 2110

Alfa AF: 0.519 Hom.: 14248

Bravo AF: 0.582

Asia WGS AF: 0.428 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.6
DANN	Benign	0.52
PhyloP100		-0.16
Mutation Taster		=99/1	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: rs456998; hg19: chr5-141025162;