rs12620053

Positions:

• chr2-166301776-C-A
• chr2-166301776-C-G

Variant summary

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

The NM_001365536.1(SCN9A):​c.901+1314G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 150,228 control chromosomes in the GnomAD database, including 27,816 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 0.60 (27816 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.901+1314G>T		intron_variant		ENST00000642356.2	NP_001352465.1
SCN1A-AS1	NR_110260.1	n.2297C>A		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.901+1314G>T		intron_variant			NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1977+5647C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.598 AC: 89773 AN: 150116 Hom.: 27792 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.579

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.598 AC: 89837 AN: 150228 Hom.: 27816 Cov.: 31 AF XY: 0.599 AC XY: 43944 AN XY: 73416

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.581

Alfa AF: 0.596 Hom.: 3980

Bravo AF: 0.600

Asia WGS AF: 0.605 AC: 2080 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.9
DANN	Benign	0.85

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: rs12620053; hg19: chr2-167158286;