2-166282470-A-C

Position:

• chr2-166282470-A-C

Variant summary

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

The NM_001365536.1(SCN9A):​c.1975-662T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,040 control chromosomes in the GnomAD database, including 44,455 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 0.76 (44455 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.1975-662T>G		intron_variant		ENST00000642356.2	NP_001352465.1
SCN1A-AS1	NR_110260.1	n.1029+5223A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.1975-662T>G		intron_variant			NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1707+5223A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114745 AN: 151922 Hom.: 44396 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.755 AC: 114864 AN: 152040 Hom.: 44455 Cov.: 31 AF XY: 0.755 AC XY: 56145 AN XY: 74322

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.754

Alfa AF: 0.675 Hom.: 3851

Bravo AF: 0.761

Asia WGS AF: 0.823 AC: 2862 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.45

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: rs6432894; hg19: chr2-167138980;