rs10171225

Variant names:

• chr2-166306139-A-G
• rs10171225
• NM_001365536.1:c.468-219T>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.468-219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,894 control chromosomes in the GnomAD database, including 6,694 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 0.27 (6694 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.468-219T>C		intron_variant	Intron 4 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.468-219T>C		intron_variant	Intron 4 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.468-219T>C		intron_variant	Intron 4 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.468-219T>C		intron_variant	Intron 4 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.468-219T>C		intron_variant	Intron 4 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.468-219T>C		intron_variant	Intron 4 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.468-219T>C		intron_variant	Intron 5 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41708 AN: 151776 Hom.: 6689 Cov.: 31

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.275 AC: 41735 AN: 151894 Hom.: 6694 Cov.: 31 AF XY: 0.269 AC XY: 20009 AN XY: 74274

African (AFR) AF: 0.447 AC: 18492 AN: 41388

American (AMR) AF: 0.191 AC: 2908 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 771 AN: 3460

East Asian (EAS) AF: 0.0923 AC: 478 AN: 5178

South Asian (SAS) AF: 0.233 AC: 1125 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2091 AN: 10568

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14990 AN: 67908

Other (OTH) AF: 0.262 AC: 551 AN: 2104

Alfa AF: 0.237 Hom.: 5590

Bravo AF: 0.279

Asia WGS AF: 0.190 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.83
PhyloP100		-0.21
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: rs10171225; hg19: chr2-167162649; COSMIC: COSV104409017;