2-166241112-A-G

Variant names:

• chr2-166241112-A-G
• rs2155878
• NM_001365536.1:c.3627+1390T>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.3627+1390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,076 control chromosomes in the GnomAD database, including 52,289 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 0.83 (52289 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 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.3627+1390T>C		intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.3594+1390T>C		intron	N/A	NP_002968.2
	SCN1A-AS1	NR_110260.1		n.612-7083A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.3627+1390T>C		intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.3627+1390T>C		intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.3594+1390T>C		intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125644 AN: 151958 Hom.: 52268 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.827 AC: 125717 AN: 152076 Hom.: 52289 Cov.: 32 AF XY: 0.827 AC XY: 61446 AN XY: 74342

African (AFR) AF: 0.736 AC: 30490 AN: 41444

American (AMR) AF: 0.857 AC: 13084 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2979 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4829 AN: 5158

South Asian (SAS) AF: 0.780 AC: 3750 AN: 4810

European-Finnish (FIN) AF: 0.887 AC: 9398 AN: 10594

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58403 AN: 68002

Other (OTH) AF: 0.824 AC: 1741 AN: 2114

Alfa AF: 0.845 Hom.: 7051

Bravo AF: 0.826

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.51
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: rs2155878; hg19: chr2-167097622;