2-166288846-T-G

Position:

• chr2-166288846-T-G

Variant summary

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

The NM_001365536.1(SCN9A):​c.1108-203A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,968 control chromosomes in the GnomAD database, including 11,179 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 0.38 (11179 hom., cov: 32)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.1108-203A>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.1108-203A>C		intron_variant			NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.1108-203A>C		intron_variant		5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.1108-203A>C		intron_variant		5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.1108-203A>C		intron_variant				ENSP00000495983.1
SCN9A	ENST00000454569.6	c.1108-203A>C		intron_variant		1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.1108-203A>C		intron_variant		1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58044 AN: 151850 Hom.: 11183 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.382 AC: 58065 AN: 151968 Hom.: 11179 Cov.: 32 AF XY: 0.379 AC XY: 28127 AN XY: 74272

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.368

Alfa AF: 0.275 Hom.: 708

Bravo AF: 0.373

Asia WGS AF: 0.355 AC: 1241 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.41

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: rs13402540; hg19: chr2-167145356;