NM_001365536.1:c.-50-2593T>A

Variant names:

• chr2-166314399-A-T
• rs11890824
• NM_001365536.1:c.-50-2593T>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.-50-2593T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,018 control chromosomes in the GnomAD database, including 31,475 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 0.64 (31475 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.-50-2593T>A		intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.-50-2593T>A		intron	N/A	NP_002968.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.-50-2593T>A		intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.-50-2593T>A		intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.-50-2593T>A		intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96730 AN: 151898 Hom.: 31453 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.637 AC: 96794 AN: 152018 Hom.: 31475 Cov.: 32 AF XY: 0.628 AC XY: 46682 AN XY: 74300

African (AFR) AF: 0.749 AC: 31069 AN: 41482

American (AMR) AF: 0.552 AC: 8432 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3472

East Asian (EAS) AF: 0.425 AC: 2194 AN: 5158

South Asian (SAS) AF: 0.543 AC: 2616 AN: 4814

European-Finnish (FIN) AF: 0.533 AC: 5633 AN: 10560

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43001 AN: 67936

Other (OTH) AF: 0.632 AC: 1331 AN: 2106

Alfa AF: 0.637 Hom.: 3902

Bravo AF: 0.640

Asia WGS AF: 0.497 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.66
PhyloP100		-0.16
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: rs11890824; hg19: chr2-167170909;