rs7597971

Variant names:

• chr2-166431662-G-A
• rs7597971
• NM_002976.4:c.2592+656C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• holoprosencephaly

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002976.4. 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
	SCN7A	NM_002976.4	MANE Select	c.2592+656C>T		intron	N/A	NP_002967.2	Q01118
	SCN7A	NR_045628.1		n.2816+656C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN7A	ENST00000643258.1	MANE Select	c.2592+656C>T		intron	N/A	ENSP00000496114.1	Q01118
	SCN7A	ENST00000441411.2	TSL:1	c.2592+656C>T		intron	N/A	ENSP00000403846.2	Q01118
	SCN7A	ENST00000424326.5	TSL:1	n.*397+656C>T		intron	N/A	ENSP00000396600.1	F8WD82

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

African (AFR) AF: 0.768 AC: 31824 AN: 41426

American (AMR) AF: 0.676 AC: 10298 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2268 AN: 3464

East Asian (EAS) AF: 0.664 AC: 3407 AN: 5130

South Asian (SAS) AF: 0.703 AC: 3385 AN: 4812

European-Finnish (FIN) AF: 0.675 AC: 7113 AN: 10544

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45836 AN: 67912

Other (OTH) AF: 0.712 AC: 1503 AN: 2110

Alfa AF: 0.683 Hom.: 67463

Bravo AF: 0.707

Asia WGS AF: 0.695 AC: 2416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.49
PhyloP100		-0.93
Mutation Taster		=100/0	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: rs7597971; hg19: chr2-167288172;