rs4286289

Variant names:

• chr2-166305201-C-A
• rs4286289
• NM_001365536.1:c.596+591G>T

Variant summary

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

The NM_001365536.1(SCN9A):​c.596+591G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,864 control chromosomes in the GnomAD database, including 40,934 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 0.73 (40934 hom., cov: 30)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.596+591G>T		intron_variant	Intron 5 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.596+591G>T		intron_variant	Intron 5 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.596+591G>T		intron_variant	Intron 5 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.596+591G>T		intron_variant	Intron 5 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.596+591G>T		intron_variant	Intron 5 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.596+591G>T		intron_variant	Intron 5 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.596+591G>T		intron_variant	Intron 6 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111171 AN: 151746 Hom.: 40894 Cov.: 30

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.733 AC: 111273 AN: 151864 Hom.: 40934 Cov.: 30 AF XY: 0.729 AC XY: 54079 AN XY: 74232

African (AFR) AF: 0.778 AC: 32234 AN: 41456

American (AMR) AF: 0.738 AC: 11248 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2575 AN: 3466

East Asian (EAS) AF: 0.581 AC: 2985 AN: 5136

South Asian (SAS) AF: 0.762 AC: 3668 AN: 4816

European-Finnish (FIN) AF: 0.629 AC: 6628 AN: 10544

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49319 AN: 67890

Other (OTH) AF: 0.755 AC: 1594 AN: 2110

Alfa AF: 0.742 Hom.: 13446

Bravo AF: 0.739

Asia WGS AF: 0.690 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.58
PhyloP100		0.12
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: rs4286289; hg19: chr2-167161711;