2-166260145-A-G

Position:

• chr2-166260145-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.3352-8260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,666 control chromosomes in the GnomAD database, including 24,908 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 0.57 (24908 hom., cov: 33)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.3352-8260T>C		intron_variant		ENST00000642356.2	NP_001352465.1
SCN1A-AS1	NR_110260.1	n.869+8233A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.3352-8260T>C		intron_variant			NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1547+8233A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86348 AN: 151548 Hom.: 24903 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.570 AC: 86379 AN: 151666 Hom.: 24908 Cov.: 33 AF XY: 0.562 AC XY: 41676 AN XY: 74096

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.583

Alfa AF: 0.605 Hom.: 6187

Bravo AF: 0.561

Asia WGS AF: 0.497 AC: 1726 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	2.7
DANN	Benign	0.85

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: rs4371369; hg19: chr2-167116655;