rs4597545

Variant names:

• chr2-166293988-G-C
• rs4597545
• NM_001365536.1:c.965+611C>G

Variant summary

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

The NM_001365536.1(SCN9A):​c.965+611C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,916 control chromosomes in the GnomAD database, including 24,924 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 0.56 (24924 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.965+611C>G		intron_variant	Intron 8 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.965+611C>G		intron_variant	Intron 8 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.965+611C>G		intron_variant	Intron 8 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.965+611C>G		intron_variant	Intron 8 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.965+611C>G		intron_variant	Intron 8 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.965+611C>G		intron_variant	Intron 8 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.965+611C>G		intron_variant	Intron 9 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84594 AN: 151796 Hom.: 24885 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.558 AC: 84697 AN: 151916 Hom.: 24924 Cov.: 32 AF XY: 0.552 AC XY: 41001 AN XY: 74242

African (AFR) AF: 0.758 AC: 31415 AN: 41442

American (AMR) AF: 0.525 AC: 8003 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1729 AN: 3464

East Asian (EAS) AF: 0.380 AC: 1963 AN: 5162

South Asian (SAS) AF: 0.434 AC: 2088 AN: 4806

European-Finnish (FIN) AF: 0.483 AC: 5087 AN: 10534

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32839 AN: 67936

Other (OTH) AF: 0.546 AC: 1152 AN: 2110

Alfa AF: 0.542 Hom.: 2836

Bravo AF: 0.567

Asia WGS AF: 0.443 AC: 1546 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.40
PhyloP100		-1.6
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: rs4597545; hg19: chr2-167150498;