2-166204799-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.4399-335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 157,104 control chromosomes in the GnomAD database, including 2,478 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 0.16 (2377 hom., cov: 32)
  • Exomes 𝑓: 0.19 (101 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN9A	NM_001365536.1	c.4399-335T>C		intron_variant		ENST00000642356.2
SCN1A-AS1	NR_110260.1	n.611+4981A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN9A	ENST00000642356.2	c.4399-335T>C		intron_variant			NM_001365536.1	P1
SCN1A-AS1	ENST00000651574.1	n.1289+4981A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24171 AN: 151970 Hom.: 2373 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.191 AC: 960 AN: 5016 Hom.: 101 Cov.: 0 AF XY: 0.194 AC XY: 522 AN XY: 2686

Gnomad4 AFR exome AF: 0.0573

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.159 AC: 24181 AN: 152088 Hom.: 2377 Cov.: 32 AF XY: 0.165 AC XY: 12278 AN XY: 74338

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.152

Alfa AF: 0.183 Hom.: 4507

Bravo AF: 0.148

Asia WGS AF: 0.240 AC: 831 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.3
Dann	Benign	0.76

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: rs16851778; hg19: chr2-167061309;