rs173683

chr5-141648480-C-G

Variant summary

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

The NM_033449.3(FCHSD1):c.577-384G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,034 control chromosomes in the GnomAD database, including 26,845 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 0.58 (26845 hom., cov: 33)
• Consequence: FCHSD1 NM_033449.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCHSD1	NM_033449.3	c.577-384G>C		intron_variant		ENST00000435817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCHSD1	ENST00000435817.7	c.577-384G>C		intron_variant		1	NM_033449.3	P1
FCHSD1	ENST00000519800.1	c.571-384G>C		intron_variant		2
FCHSD1	ENST00000522783.5	c.571-384G>C		intron_variant		5
FCHSD1	ENST00000522126.5	c.349-384G>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88570 AN: 151916 Hom.: 26811 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.583 AC: 88661 AN: 152034 Hom.: 26845 Cov.: 33 AF XY: 0.579 AC XY: 43028 AN XY: 74324

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.563

Alfa AF: 0.573 Hom.: 3184

Bravo AF: 0.594

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.6
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs173683; hg19: chr5-141028047;