rs6721003

Positions:

• chr2-166367002-A-G

Variant summary

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

The NM_001365536.1(SCN9A):​c.-51+8695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,032 control chromosomes in the GnomAD database, including 27,725 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 0.59 (27725 hom., cov: 33)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.-51+8695T>C		intron_variant		ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.-51+8695T>C		intron_variant			NM_001365536.1	ENSP00000495601	P1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88978 AN: 151914 Hom.: 27675 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.586 AC: 89081 AN: 152032 Hom.: 27725 Cov.: 33 AF XY: 0.575 AC XY: 42750 AN XY: 74328

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.547

Alfa AF: 0.533 Hom.: 35520

Bravo AF: 0.598

Asia WGS AF: 0.382 AC: 1327 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.82

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: rs6721003; hg19: chr2-167223512;