rs10930214

chr2-166249343-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.3472+2422G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,932 control chromosomes in the GnomAD database, including 34,126 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 0.67 (34122 hom., cov: 32)
  • Exomes 𝑓: 0.83 (4 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN9A	NM_001365536.1	c.3472+2422G>C		intron_variant		ENST00000642356.2
SCN1A-AS1	NR_110260.1	n.694C>G		splice_region_variant, non_coding_transcript_exon_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN9A	ENST00000642356.2	c.3472+2422G>C		intron_variant			NM_001365536.1	P1
SCN1A-AS1	ENST00000651574.1	n.1372C>G		splice_region_variant, non_coding_transcript_exon_variant	13/19

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101024 AN: 151802 Hom.: 34110 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.833 AC: 10 AN: 12 Hom.: 4 Cov.: 0 AF XY: 0.833 AC XY: 10 AN XY: 12

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.665 AC: 101071 AN: 151920 Hom.: 34122 Cov.: 32 AF XY: 0.655 AC XY: 48623 AN XY: 74214

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.670

Alfa AF: 0.698 Hom.: 4616

Bravo AF: 0.658

Asia WGS AF: 0.525 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.57
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10930214; hg19: chr2-167105853;