rs6432893

Variant names:

• chr2-166280609-G-A
• rs6432893
• NM_001365536.1:c.2105-14C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166280609-G-A
• chr2-166280609-G-T
• chr2-166280609-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365536.1(SCN9A):​c.2105-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,494,214 control chromosomes in the GnomAD database, including 182,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24870 hom., cov: 33)
  • Exomes 𝑓: 0.48 (157759 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -0.857
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-166280609-G-A is Benign according to our data. Variant chr2-166280609-G-A is described in ClinVar as Benign. ClinVar VariationId is 167659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.2105-14C>T		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.2072-14C>T		intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.1029+3362G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.2105-14C>T		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.2105-14C>T		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.2072-14C>T		intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84640 AN: 151914 Hom.: 24832 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.493 AC: 79755 AN: 161820 AF XY: 0.484

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.376

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.482 AC: 646768 AN: 1342182 Hom.: 157759 Cov.: 21 AF XY: 0.480 AC XY: 319087 AN XY: 665116

African (AFR) AF: 0.767 AC: 23397 AN: 30506

American (AMR) AF: 0.526 AC: 18618 AN: 35402

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 12348 AN: 24412

East Asian (EAS) AF: 0.383 AC: 13997 AN: 36580

South Asian (SAS) AF: 0.442 AC: 34174 AN: 77370

European-Finnish (FIN) AF: 0.482 AC: 23793 AN: 49332

Middle Eastern (MID) AF: 0.458 AC: 2539 AN: 5546

European-Non Finnish (NFE) AF: 0.477 AC: 490303 AN: 1027006

Other (OTH) AF: 0.493 AC: 27599 AN: 56028

GnomAD4 genome AF: 0.557 AC: 84741 AN: 152032 Hom.: 24870 Cov.: 33 AF XY: 0.552 AC XY: 41049 AN XY: 74308

African (AFR) AF: 0.754 AC: 31281 AN: 41502

American (AMR) AF: 0.525 AC: 8013 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1734 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1945 AN: 5146

South Asian (SAS) AF: 0.436 AC: 2106 AN: 4828

European-Finnish (FIN) AF: 0.486 AC: 5130 AN: 10548

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.485 AC: 32956 AN: 67958

Other (OTH) AF: 0.545 AC: 1153 AN: 2114

Alfa AF: 0.449 Hom.: 2281

Bravo AF: 0.566

Asia WGS AF: 0.444 AC: 1551 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Channelopathy-associated congenital insensitivity to pain, autosomal recessive (2)
-	-	2	not provided (2)
-	-	2	Paroxysmal extreme pain disorder (2)
-	-	2	Primary erythromelalgia (2)
-	-	1	Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)
-	-	1	Inherited Erythromelalgia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.53
PhyloP100		-0.86
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: rs6432893; hg19: chr2-167137119; COSMIC: COSV57600629; COSMIC: COSV57600629;