rs7607967

Variant names:

• chr2-166256826-A-G
• rs7607967
• NM_001365536.1:c.3352-4941T>C

Variant summary

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

The NM_001365536.1(SCN9A):​c.3352-4941T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,294 control chromosomes in the GnomAD database, including 24,677 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 0.57 (24677 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• Publications: 9 publications found

Genes affected

SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

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 (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. 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
	SCN9A	NM_001365536.1	MANE Select	c.3352-4941T>C		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.3319-4941T>C		intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.869+4914A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.3352-4941T>C		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.3352-4941T>C		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.3319-4941T>C		intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85668 AN: 151178 Hom.: 24675 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.566 AC: 85687 AN: 151294 Hom.: 24677 Cov.: 31 AF XY: 0.559 AC XY: 41328 AN XY: 73922

African (AFR) AF: 0.589 AC: 24306 AN: 41294

American (AMR) AF: 0.425 AC: 6430 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1830 AN: 3462

East Asian (EAS) AF: 0.447 AC: 2287 AN: 5120

South Asian (SAS) AF: 0.496 AC: 2386 AN: 4812

European-Finnish (FIN) AF: 0.574 AC: 6055 AN: 10556

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40571 AN: 67612

Other (OTH) AF: 0.550 AC: 1156 AN: 2102

Alfa AF: 0.583 Hom.: 68595

Bravo AF: 0.558

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.70
PhyloP100		0.92
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: rs7607967; hg19: chr2-167113336;