2-166303436-C-T

Position:

• chr2-166303436-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365536.1(SCN9A):​c.689-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 660,158 control chromosomes in the GnomAD database, including 57,326 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 0.37 (11169 hom., cov: 32)
  • Exomes 𝑓: 0.42 (46157 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.689-134G>A		intron_variant		ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.689-134G>A		intron_variant			NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1977+7307C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55871 AN: 151844 Hom.: 11173 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.416 AC: 211447 AN: 508196 Hom.: 46157 AF XY: 0.417 AC XY: 112432 AN XY: 269894

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.368 AC: 55879 AN: 151962 Hom.: 11169 Cov.: 32 AF XY: 0.366 AC XY: 27142 AN XY: 74234

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.363

Alfa AF: 0.421 Hom.: 12892

Bravo AF: 0.347

Asia WGS AF: 0.299 AC: 1042 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	1.6
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs13017637; hg19: chr2-167159946; COSMIC: COSV104409013; COSMIC: COSV104409013;