rs75230218

Variant names:

• chr2-166233466-T-A
• rs75230218
• NM_001365536.1:c.3802-4A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166233466-T-A
• chr2-166233466-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001365536.1(SCN9A):​c.3802-4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000426 in 1,407,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: SCN9A NM_001365536.1 splice_region, intron
• Scores: Splicing: ADA: 0.0001977
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.3802-4A>T		splice_region_variant, intron_variant	Intron 20 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.3802-4A>T		splice_region_variant, intron_variant	Intron 20 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.3802-4A>T		splice_region_variant, intron_variant	Intron 20 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.3769-4A>T		splice_region_variant, intron_variant	Intron 20 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.3769-4A>T		splice_region_variant, intron_variant	Intron 20 of 26			ENSP00000495983.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000426 AC: 6 AN: 1407256 Hom.: 0 Cov.: 28 AF XY: 0.00000572 AC XY: 4 AN XY: 698910

African (AFR) AF: 0.00 AC: 0 AN: 29926

American (AMR) AF: 0.00 AC: 0 AN: 29424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24322

East Asian (EAS) AF: 0.00 AC: 0 AN: 37874

South Asian (SAS) AF: 0.00 AC: 0 AN: 74748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00000548 AC: 6 AN: 1094398

Other (OTH) AF: 0.00 AC: 0 AN: 58146

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		-0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00020
dbscSNV1_RF	Benign	0.0040
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: rs75230218; hg19: chr2-167089976;