chr2-166267711-A-T

Variant names:

• chr2-166267711-A-T
• rs4443014
• NM_001365536.1:c.3351+4688T>A

Variant summary

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

The NM_001365536.1(SCN9A):​c.3351+4688T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 151,768 control chromosomes in the GnomAD database, including 41,899 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 0.74 (41899 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.3351+4688T>A		intron_variant	Intron 17 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.3351+4688T>A		intron_variant	Intron 17 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.3351+4688T>A		intron_variant	Intron 17 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.3318+4688T>A		intron_variant	Intron 17 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.3318+4688T>A		intron_variant	Intron 17 of 26			ENSP00000495983.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112351 AN: 151650 Hom.: 41890 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.741 AC: 112404 AN: 151768 Hom.: 41899 Cov.: 31 AF XY: 0.739 AC XY: 54784 AN XY: 74158

African (AFR) AF: 0.722 AC: 29892 AN: 41402

American (AMR) AF: 0.596 AC: 9044 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2758 AN: 3468

East Asian (EAS) AF: 0.787 AC: 4036 AN: 5130

South Asian (SAS) AF: 0.748 AC: 3600 AN: 4812

European-Finnish (FIN) AF: 0.809 AC: 8553 AN: 10578

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52024 AN: 67882

Other (OTH) AF: 0.738 AC: 1557 AN: 2110

Alfa AF: 0.751 Hom.: 5068

Bravo AF: 0.727

Asia WGS AF: 0.747 AC: 2598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.63
DANN	Benign	0.32
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: rs4443014; hg19: chr2-167124221;