chr2-166288846-T-G

Variant names:

• chr2-166288846-T-G
• rs13402540
• NM_001365536.1:c.1108-203A>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.1108-203A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,968 control chromosomes in the GnomAD database, including 11,179 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 0.38 (11179 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 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.1108-203A>C		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.1108-203A>C		intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.1030-5719T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.1108-203A>C		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.1108-203A>C		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.1108-203A>C		intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58044 AN: 151850 Hom.: 11183 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.382 AC: 58065 AN: 151968 Hom.: 11179 Cov.: 32 AF XY: 0.379 AC XY: 28127 AN XY: 74272

African (AFR) AF: 0.384 AC: 15910 AN: 41462

American (AMR) AF: 0.318 AC: 4839 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1610 AN: 5176

South Asian (SAS) AF: 0.358 AC: 1725 AN: 4822

European-Finnish (FIN) AF: 0.414 AC: 4359 AN: 10528

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.403 AC: 27375 AN: 67958

Other (OTH) AF: 0.368 AC: 777 AN: 2110

Alfa AF: 0.282 Hom.: 769

Bravo AF: 0.373

Asia WGS AF: 0.355 AC: 1241 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.41
PhyloP100		0.28
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: rs13402540; hg19: chr2-167145356;