2-166350573-A-G

Variant names:

• chr2-166350573-A-G
• rs1540871
• NM_001365536.1:c.-51+25124T>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.-51+25124T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,030 control chromosomes in the GnomAD database, including 29,201 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 0.62 (29201 hom., cov: 33)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.-51+25124T>C		intron_variant	Intron 1 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.-51+25124T>C		intron_variant	Intron 1 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.-51+25131T>C		intron_variant	Intron 1 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.-51+25124T>C		intron_variant	Intron 1 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.-51+25131T>C		intron_variant	Intron 1 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.-51+25124T>C		intron_variant	Intron 1 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.-128+25162T>C		intron_variant	Intron 1 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93510 AN: 151918 Hom.: 29163 Cov.: 33

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.616 AC: 93598 AN: 152030 Hom.: 29201 Cov.: 33 AF XY: 0.611 AC XY: 45394 AN XY: 74290

African (AFR) AF: 0.727 AC: 30136 AN: 41478

American (AMR) AF: 0.566 AC: 8643 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2414 AN: 5170

South Asian (SAS) AF: 0.549 AC: 2650 AN: 4826

European-Finnish (FIN) AF: 0.522 AC: 5500 AN: 10546

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40004 AN: 67952

Other (OTH) AF: 0.630 AC: 1328 AN: 2108

Alfa AF: 0.599 Hom.: 9920

Bravo AF: 0.624

Asia WGS AF: 0.544 AC: 1889 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.33
PhyloP100		-0.63
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: rs1540871; hg19: chr2-167207083;