rs7597971

Positions:

• chr2-166431662-G-A

Variant summary

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

The NM_002976.4(SCN7A):​c.2592+656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,844 control chromosomes in the GnomAD database, including 37,579 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 0.70 (37579 hom., cov: 31)
• Consequence: SCN7A NM_002976.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

Genes affected

SCN7A (HGNC:10594): (sodium voltage-gated channel alpha subunit 7) This gene encodes one of the many voltage-gated sodium channel proteins. For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer positive charged residues that in other sodium channels; domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. Several alternatively spliced transcript variants exist, but the full-length natures of all of them remain unknown. [provided by RefSeq, Dec 2011]

SCN7A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN7A	NM_002976.4	c.2592+656C>T		intron_variant		ENST00000643258.1	NP_002967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN7A	ENST00000643258.1	c.2592+656C>T		intron_variant			NM_002976.4	ENSP00000496114.1
SCN7A	ENST00000441411.2	c.2592+656C>T		intron_variant		1		ENSP00000403846.2
SCN7A	ENST00000424326.5	n.*397+656C>T		intron_variant		1		ENSP00000396600.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106463 AN: 151724 Hom.: 37538 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.702 AC: 106557 AN: 151844 Hom.: 37579 Cov.: 31 AF XY: 0.700 AC XY: 51932 AN XY: 74202

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.712

Alfa AF: 0.681 Hom.: 48361

Bravo AF: 0.707

Asia WGS AF: 0.695 AC: 2416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.49

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: rs7597971; hg19: chr2-167288172;