2-166297279-T-C

Variant names:

• chr2-166297279-T-C
• rs11688164
• NM_001365536.1:c.902-2617A>G

Variant summary

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

The NM_001365536.1(SCN9A):​c.902-2617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 146,060 control chromosomes in the GnomAD database, including 4,784 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 0.23 (4784 hom., cov: 27)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.902-2617A>G		intron_variant	Intron 7 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.902-2617A>G		intron_variant	Intron 7 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.902-2617A>G		intron_variant	Intron 7 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.902-2617A>G		intron_variant	Intron 7 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.902-2617A>G		intron_variant	Intron 7 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.902-2617A>G		intron_variant	Intron 7 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.902-2617A>G		intron_variant	Intron 8 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 33695 AN: 145970 Hom.: 4782 Cov.: 27

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.231 AC: 33734 AN: 146060 Hom.: 4784 Cov.: 27 AF XY: 0.235 AC XY: 16667 AN XY: 70774

African (AFR) AF: 0.384 AC: 15029 AN: 39172

American (AMR) AF: 0.237 AC: 3410 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 606 AN: 3438

East Asian (EAS) AF: 0.423 AC: 2085 AN: 4930

South Asian (SAS) AF: 0.242 AC: 1119 AN: 4622

European-Finnish (FIN) AF: 0.198 AC: 1810 AN: 9126

Middle Eastern (MID) AF: 0.207 AC: 55 AN: 266

European-Non Finnish (NFE) AF: 0.135 AC: 9087 AN: 67172

Other (OTH) AF: 0.205 AC: 416 AN: 2028

Alfa AF: 0.174 Hom.: 5192

Bravo AF: 0.241

Asia WGS AF: 0.304 AC: 1054 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.59
PhyloP100		0.15
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: rs11688164; hg19: chr2-167153789;