2-166261532-T-C

Position:

• chr2-166261532-T-C

Variant summary

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

The NM_001365536.1(SCN9A):​c.3352-9647A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 151,952 control chromosomes in the GnomAD database, including 63,547 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 0.91 (63547 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN9A	NM_001365536.1	c.3352-9647A>G		intron_variant		ENST00000642356.2
SCN1A-AS1	NR_110260.1	n.869+9620T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN9A	ENST00000642356.2	c.3352-9647A>G		intron_variant			NM_001365536.1	P1
SCN1A-AS1	ENST00000651574.1	n.1547+9620T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138731 AN: 151834 Hom.: 63496 Cov.: 31

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.914 AC: 138840 AN: 151952 Hom.: 63547 Cov.: 31 AF XY: 0.914 AC XY: 67891 AN XY: 74264

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.902

Alfa AF: 0.906 Hom.: 15276

Bravo AF: 0.917

Asia WGS AF: 0.903 AC: 3142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.50

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: rs4561679; hg19: chr2-167118042;