chr2-166304910-G-A

Variant names:

• chr2-166304910-G-A
• rs6432896
• NM_001365536.1:c.597-581C>T

Variant summary

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

The NM_001365536.1(SCN9A):​c.597-581C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,852 control chromosomes in the GnomAD database, including 20,373 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 0.52 (20373 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 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.597-581C>T		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.597-581C>T		intron	N/A	NP_002968.2	Q15858-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.597-581C>T		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.597-581C>T		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.597-581C>T		intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78263 AN: 151734 Hom.: 20365 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.516 AC: 78305 AN: 151852 Hom.: 20373 Cov.: 31 AF XY: 0.517 AC XY: 38348 AN XY: 74238

African (AFR) AF: 0.507 AC: 21012 AN: 41428

American (AMR) AF: 0.430 AC: 6552 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3423 AN: 5146

South Asian (SAS) AF: 0.587 AC: 2821 AN: 4808

European-Finnish (FIN) AF: 0.550 AC: 5804 AN: 10544

Middle Eastern (MID) AF: 0.628 AC: 182 AN: 290

European-Non Finnish (NFE) AF: 0.518 AC: 35182 AN: 67926

Other (OTH) AF: 0.518 AC: 1088 AN: 2102

Alfa AF: 0.517 Hom.: 25441

Bravo AF: 0.510

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.56
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6432896;

hg19: chr2-167161420;