2-166269944-A-T

Variant names:

• chr2-166269944-A-T
• rs4453709
• NM_001365536.1:c.3351+2455T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365536.1(SCN9A):​c.3351+2455T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,832 control chromosomes in the GnomAD database, including 13,293 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 0.41 (13293 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.3351+2455T>A		intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.3318+2455T>A		intron	N/A	NP_002968.2
	SCN1A-AS1	NR_110260.1		n.870-7144A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.3351+2455T>A		intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.3351+2455T>A		intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.3318+2455T>A		intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62569 AN: 151714 Hom.: 13259 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.413 AC: 62658 AN: 151832 Hom.: 13293 Cov.: 32 AF XY: 0.418 AC XY: 30988 AN XY: 74166

African (AFR) AF: 0.417 AC: 17274 AN: 41454

American (AMR) AF: 0.531 AC: 8086 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2721 AN: 5132

South Asian (SAS) AF: 0.381 AC: 1836 AN: 4816

European-Finnish (FIN) AF: 0.428 AC: 4505 AN: 10518

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25254 AN: 67892

Other (OTH) AF: 0.418 AC: 881 AN: 2108

Alfa AF: 0.395 Hom.: 1497

Bravo AF: 0.422

Asia WGS AF: 0.437 AC: 1519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.18
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4453709; hg19: chr2-167126454;