rs9287868

Variant names:

• chr2-166570889-A-C
• rs9287868
• ENST00000650747.1:c.-223-706T>G

Variant summary

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

The ENST00000650747.1(SCN7A):​c.-223-706T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 152,310 control chromosomes in the GnomAD database, including 211 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 0.043 (211 hom., cov: 33)
• Consequence: SCN7A ENST00000650747.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 1 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]

LOC107985958 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107985958	XR_001739762.1	n.173-706T>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN7A	ENST00000650747.1	c.-223-706T>G		intron_variant	Intron 2 of 4			ENSP00000498959.1

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 6530 AN: 152192 Hom.: 212 Cov.: 33

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0478

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

GnomAD4 genome AF: 0.0429 AC: 6536 AN: 152310 Hom.: 211 Cov.: 33 AF XY: 0.0425 AC XY: 3165 AN XY: 74474

African (AFR) AF: 0.0794 AC: 3301 AN: 41578

American (AMR) AF: 0.0277 AC: 424 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0669 AC: 323 AN: 4828

European-Finnish (FIN) AF: 0.00951 AC: 101 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0295 AC: 2005 AN: 68016

Other (OTH) AF: 0.0473 AC: 100 AN: 2114

Alfa AF: 0.0388 Hom.: 17

Bravo AF: 0.0450

Asia WGS AF: 0.0300 AC: 104 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.51
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9287868; hg19: chr2-167427399;