chr2-166230351-A-T

Variant names:

• chr2-166230351-A-T
• rs10170041
• NM_001365536.1:c.3925-1379T>A

Variant summary

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

The NM_001365536.1(SCN9A):​c.3925-1379T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,896 control chromosomes in the GnomAD database, including 24,679 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 (24679 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 0 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=-0.84).
• 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.3925-1379T>A		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.3892-1379T>A		intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.612-17844A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.3925-1379T>A		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.3925-1379T>A		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.3892-1379T>A		intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85822 AN: 151778 Hom.: 24676 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.565 AC: 85847 AN: 151896 Hom.: 24679 Cov.: 31 AF XY: 0.558 AC XY: 41442 AN XY: 74230

African (AFR) AF: 0.585 AC: 24222 AN: 41412

American (AMR) AF: 0.420 AC: 6412 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1903 AN: 3472

East Asian (EAS) AF: 0.440 AC: 2256 AN: 5126

South Asian (SAS) AF: 0.496 AC: 2386 AN: 4806

European-Finnish (FIN) AF: 0.573 AC: 6041 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40794 AN: 67954

Other (OTH) AF: 0.551 AC: 1161 AN: 2106

Alfa AF: 0.597 Hom.: 3358

Bravo AF: 0.555

Asia WGS AF: 0.475 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		0.49
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: rs10170041; hg19: chr2-167086861;