2-166305088-G-A

Position:

• chr2-166305088-G-A

Variant summary

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

The NM_001365536.1(SCN9A):​c.596+704C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 151,864 control chromosomes in the GnomAD database, including 51,310 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 0.82 (51310 hom., cov: 29)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.596+704C>T		intron_variant		ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.596+704C>T		intron_variant			NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1977+8959G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124473 AN: 151746 Hom.: 51253 Cov.: 29

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.820 AC: 124592 AN: 151864 Hom.: 51310 Cov.: 29 AF XY: 0.820 AC XY: 60851 AN XY: 74224

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.812

Alfa AF: 0.803 Hom.: 45308

Bravo AF: 0.823

Asia WGS AF: 0.834 AC: 2898 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4605385; hg19: chr2-167161598;