rs12622743

Variant names:

• chr2-166337881-A-G
• rs12622743
• NM_001365536.1:c.-50-26075T>C

Variant summary

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

The NM_001365536.1(SCN9A):​c.-50-26075T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,098 control chromosomes in the GnomAD database, including 1,953 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 0.16 (1953 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.-50-26075T>C		intron_variant	Intron 1 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.-50-26075T>C		intron_variant	Intron 1 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.-50-26075T>C		intron_variant	Intron 1 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.-50-26075T>C		intron_variant	Intron 1 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.-50-26075T>C		intron_variant	Intron 1 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.-50-26075T>C		intron_variant	Intron 1 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.-127-16366T>C		intron_variant	Intron 1 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24096 AN: 151980 Hom.: 1947 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.159 AC: 24128 AN: 152098 Hom.: 1953 Cov.: 32 AF XY: 0.161 AC XY: 11948 AN XY: 74340

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.152

Alfa AF: 0.153 Hom.: 456

Bravo AF: 0.162

Asia WGS AF: 0.160 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.60
DANN	Benign	0.66

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: rs12622743; hg19: chr2-167194391;