chr2-166196032-C-T

Variant names:

• chr2-166196032-C-T
• rs13396526
• NM_001365536.1:c.*2640G>A

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.*2640G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,920 control chromosomes in the GnomAD database, including 14,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14538 hom., cov: 32)
  • Exomes 𝑓: 0.65 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCN9A NM_001365536.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.34
• Publications: 4 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=-1.04).
• BP6: Variant 2-166196032-C-T is Benign according to our data. Variant chr2-166196032-C-T is described in ClinVar as Benign. ClinVar VariationId is 331907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 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.*2640G>A		3_prime_UTR	Exon 27 of 27	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.*2640G>A		3_prime_UTR	Exon 27 of 27	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.432-3607C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.*2640G>A		3_prime_UTR	Exon 27 of 27	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.*2640G>A		3_prime_UTR	Exon 27 of 27	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.*2640G>A		3_prime_UTR	Exon 27 of 27	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65799 AN: 151802 Hom.: 14541 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.433

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.654 AC: 17 AN: 26 Hom.: 5 Cov.: 0 AF XY: 0.611 AC XY: 11 AN XY: 18

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.650 AC: 13 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.433 AC: 65806 AN: 151920 Hom.: 14538 Cov.: 32 AF XY: 0.430 AC XY: 31906 AN XY: 74242

African (AFR) AF: 0.386 AC: 16003 AN: 41430

American (AMR) AF: 0.334 AC: 5103 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1638 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2227 AN: 5160

South Asian (SAS) AF: 0.469 AC: 2259 AN: 4812

European-Finnish (FIN) AF: 0.458 AC: 4813 AN: 10510

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32334 AN: 67948

Other (OTH) AF: 0.432 AC: 913 AN: 2114

Alfa AF: 0.461 Hom.: 2030

Bravo AF: 0.423

Asia WGS AF: 0.447 AC: 1556 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Channelopathy-associated congenital insensitivity to pain, autosomal recessive (1)
-	-	1	not provided (1)
-	-	1	Paroxysmal extreme pain disorder (1)
-	-	1	Primary erythromelalgia (1)
-	-	1	Small fiber neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.48
PhyloP100		-4.3
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: rs13396526; hg19: chr2-167052542; COSMIC: COSV109426151; COSMIC: COSV109426151;