rs4371369

Variant names:

• chr2-166260145-A-G
• rs4371369
• NM_001365536.1:c.3352-8260T>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.3352-8260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,666 control chromosomes in the GnomAD database, including 24,908 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 (24908 hom., cov: 33)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 6 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 = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.3352-8260T>C		intron_variant	Intron 17 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.3352-8260T>C		intron_variant	Intron 17 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.3352-8260T>C		intron_variant	Intron 17 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.3319-8260T>C		intron_variant	Intron 17 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.3319-8260T>C		intron_variant	Intron 17 of 26			ENSP00000495983.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86348 AN: 151548 Hom.: 24903 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.570 AC: 86379 AN: 151666 Hom.: 24908 Cov.: 33 AF XY: 0.562 AC XY: 41676 AN XY: 74096

African (AFR) AF: 0.553 AC: 22910 AN: 41418

American (AMR) AF: 0.448 AC: 6795 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2239 AN: 3466

East Asian (EAS) AF: 0.440 AC: 2258 AN: 5134

South Asian (SAS) AF: 0.552 AC: 2660 AN: 4818

European-Finnish (FIN) AF: 0.574 AC: 6064 AN: 10558

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.612 AC: 41502 AN: 67784

Other (OTH) AF: 0.583 AC: 1232 AN: 2114

Alfa AF: 0.605 Hom.: 6321

Bravo AF: 0.561

Asia WGS AF: 0.497 AC: 1726 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.85
PhyloP100		0.076
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: rs4371369; hg19: chr2-167116655;