2-166240054-T-C

Variant names:

• chr2-166240054-T-C
• rs12621853
• NM_001365536.1:c.3628-1787A>G

Variant summary

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

The NM_001365536.1(SCN9A):​c.3628-1787A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,242 control chromosomes in the GnomAD database, including 1,796 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 0.14 (1796 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.3628-1787A>G		intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.3595-1787A>G		intron	N/A	NP_002968.2
	SCN1A-AS1	NR_110260.1		n.612-8141T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.3628-1787A>G		intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.3628-1787A>G		intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.3595-1787A>G		intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20782 AN: 152122 Hom.: 1793 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.137 AC: 20792 AN: 152242 Hom.: 1796 Cov.: 32 AF XY: 0.143 AC XY: 10621 AN XY: 74438

African (AFR) AF: 0.0484 AC: 2014 AN: 41586

American (AMR) AF: 0.136 AC: 2084 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1747 AN: 5142

South Asian (SAS) AF: 0.195 AC: 940 AN: 4828

European-Finnish (FIN) AF: 0.235 AC: 2498 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10486 AN: 67996

Other (OTH) AF: 0.132 AC: 279 AN: 2112

Alfa AF: 0.147 Hom.: 875

Bravo AF: 0.127

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.023
DANN	Benign	0.47
PhyloP100		-2.8
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: rs12621853; hg19: chr2-167096564;