chr2-166325017-A-G

Variant names:

• chr2-166325017-A-G
• rs11898284
• NM_001365536.1:c.-50-13211T>C

Variant summary

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

The NM_001365536.1(SCN9A):​c.-50-13211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,178 control chromosomes in the GnomAD database, including 1,730 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 0.15 (1730 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 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.-50-13211T>C		intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.-50-13211T>C		intron	N/A	NP_002968.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.-50-13211T>C		intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.-50-13211T>C		intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.-50-13211T>C		intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22701 AN: 152060 Hom.: 1731 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.149 AC: 22711 AN: 152178 Hom.: 1730 Cov.: 32 AF XY: 0.152 AC XY: 11276 AN XY: 74394

African (AFR) AF: 0.133 AC: 5517 AN: 41518

American (AMR) AF: 0.184 AC: 2815 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.179 AC: 923 AN: 5158

South Asian (SAS) AF: 0.154 AC: 744 AN: 4828

European-Finnish (FIN) AF: 0.165 AC: 1754 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10061 AN: 67986

Other (OTH) AF: 0.145 AC: 307 AN: 2114

Alfa AF: 0.150 Hom.: 244

Bravo AF: 0.150

Asia WGS AF: 0.154 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.35
PhyloP100		0.75
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: rs11898284; hg19: chr2-167181527;