rs6754031

Variant names:

• chr2-166298928-T-G
• rs6754031
• NM_001365536.1:c.901+4162A>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.901+4162A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,846 control chromosomes in the GnomAD database, including 10,965 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 0.38 (10964 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.901+4162A>C		intron_variant	Intron 7 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.901+4162A>C		intron_variant	Intron 7 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.901+4162A>C		intron_variant	Intron 7 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.901+4162A>C		intron_variant	Intron 7 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.901+4162A>C		intron_variant	Intron 7 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.901+4162A>C		intron_variant	Intron 7 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.901+4162A>C		intron_variant	Intron 8 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57596 AN: 151726 Hom.: 10968 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.379 AC: 57616 AN: 151844 Hom.: 10964 Cov.: 33 AF XY: 0.376 AC XY: 27899 AN XY: 74214

African (AFR) AF: 0.377 AC: 15619 AN: 41376

American (AMR) AF: 0.317 AC: 4846 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3466

East Asian (EAS) AF: 0.312 AC: 1614 AN: 5176

South Asian (SAS) AF: 0.357 AC: 1715 AN: 4810

European-Finnish (FIN) AF: 0.410 AC: 4312 AN: 10526

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27265 AN: 67892

Other (OTH) AF: 0.367 AC: 777 AN: 2116

Alfa AF: 0.407 Hom.: 1625

Bravo AF: 0.371

Asia WGS AF: 0.352 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		-0.076
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: rs6754031; hg19: chr2-167155438;