rs7637849

Positions:

• chr3-38617784-G-A
• chr3-38617784-G-T

Variant summary

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

The NM_001099404.2(SCN5A):​c.611+3059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 152,070 control chromosomes in the GnomAD database, including 988 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 0.070 (988 hom., cov: 32)
• Consequence: SCN5A NM_001099404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

Genes affected

SCN5A (HGNC:10593): (sodium voltage-gated channel alpha subunit 5) The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene have been associated with long QT syndrome type 3 (LQT3), atrial fibrillation, cardiomyopathy, and Brugada syndrome 1, all autosomal dominant cardiac diseases. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN5A	NM_000335.5	c.611+3059C>T		intron_variant		ENST00000423572.7
SCN5A	NM_001099404.2	c.611+3059C>T		intron_variant		ENST00000413689.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN5A	ENST00000413689.6	c.611+3059C>T		intron_variant		5	NM_001099404.2	P4
SCN5A	ENST00000423572.7	c.611+3059C>T		intron_variant		1	NM_000335.5	A1

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10598 AN: 151952 Hom.: 988 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.0633

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

GnomAD4 genome AF: 0.0699 AC: 10628 AN: 152070 Hom.: 988 Cov.: 32 AF XY: 0.0701 AC XY: 5210 AN XY: 74336

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0832

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.0410

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.0627

Alfa AF: 0.0252 Hom.: 43

Bravo AF: 0.0804

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.63

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: rs7637849; hg19: chr3-38659275;