2-166294304-T-C

Variant names:

• chr2-166294304-T-C
• rs4387806
• NM_001365536.1:c.965+295A>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+295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,026 control chromosomes in the GnomAD database, including 44,062 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 0.75 (44062 hom., cov: 30)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.965+295A>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+295A>G		intron_variant	Intron 8 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.965+295A>G		intron_variant	Intron 8 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.965+295A>G		intron_variant	Intron 8 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.965+295A>G		intron_variant	Intron 8 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.965+295A>G		intron_variant	Intron 8 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.965+295A>G		intron_variant	Intron 9 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114257 AN: 151908 Hom.: 44015 Cov.: 30

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.752 AC: 114362 AN: 152026 Hom.: 44062 Cov.: 30 AF XY: 0.752 AC XY: 55866 AN XY: 74286

African (AFR) AF: 0.926 AC: 38441 AN: 41504

American (AMR) AF: 0.684 AC: 10439 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2504 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4404 AN: 5160

South Asian (SAS) AF: 0.768 AC: 3698 AN: 4812

European-Finnish (FIN) AF: 0.694 AC: 7330 AN: 10564

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.667 AC: 45317 AN: 67948

Other (OTH) AF: 0.749 AC: 1575 AN: 2102

Alfa AF: 0.636 Hom.: 2047

Bravo AF: 0.758

Asia WGS AF: 0.821 AC: 2858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-1.8
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: rs4387806; hg19: chr2-167150814;