rs17748381

Variant names:

• chr2-166239974-A-G
• rs17748381
• NM_001365536.1:c.3628-1707T>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.3628-1707T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 152,212 control chromosomes in the GnomAD database, including 706 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 0.093 (706 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.3628-1707T>C		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.3595-1707T>C		intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.612-8221A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.3628-1707T>C		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.3628-1707T>C		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.3595-1707T>C		intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14093 AN: 152094 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.0927 AC: 14107 AN: 152212 Hom.: 706 Cov.: 32 AF XY: 0.0898 AC XY: 6687 AN XY: 74426

African (AFR) AF: 0.0841 AC: 3492 AN: 41526

American (AMR) AF: 0.0908 AC: 1388 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.0123 AC: 64 AN: 5186

South Asian (SAS) AF: 0.0770 AC: 371 AN: 4820

European-Finnish (FIN) AF: 0.0770 AC: 817 AN: 10610

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6952 AN: 67988

Other (OTH) AF: 0.113 AC: 239 AN: 2116

Alfa AF: 0.0974 Hom.: 100

Bravo AF: 0.0931

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.65
PhyloP100		0.27
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: rs17748381; hg19: chr2-167096484;