rs11898284

Positions:

• chr2-166325017-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365536.1(SCN9A):​c.-50-13211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,178 control chromosomes in the GnomAD database, including 1,730 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 0.15 (1730 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.-50-13211T>C		intron_variant		ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.-50-13211T>C		intron_variant			NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1978-26580A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22701 AN: 152060 Hom.: 1731 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.149 AC: 22711 AN: 152178 Hom.: 1730 Cov.: 32 AF XY: 0.152 AC XY: 11276 AN XY: 74394

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.145

Alfa AF: 0.151 Hom.: 237

Bravo AF: 0.150

Asia WGS AF: 0.154 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs11898284; hg19: chr2-167181527;