2-166226468-T-C

Variant names:

• chr2-166226468-T-C
• rs7595255
• NM_001365536.1:c.4398+99A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001365536.1(SCN9A):​c.4398+99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 788,272 control chromosomes in the GnomAD database, including 303,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.88 (59240 hom., cov: 33)
  • Exomes 𝑓: 0.87 (243795 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-166226468-T-C is Benign according to our data. Variant chr2-166226468-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.4398+99A>G		intron_variant	Intron 24 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.4398+99A>G		intron_variant	Intron 24 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.4398+99A>G		intron_variant	Intron 24 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.4365+99A>G		intron_variant	Intron 24 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.4365+99A>G		intron_variant	Intron 24 of 26			ENSP00000495983.1

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134102 AN: 152052 Hom.: 59200 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.882

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.873

GnomAD4 exome AF: 0.875 AC: 556485 AN: 636102 Hom.: 243795 AF XY: 0.874 AC XY: 283491 AN XY: 324324

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.897

Gnomad4 ASJ exome AF: 0.909

Gnomad4 EAS exome AF: 0.951

Gnomad4 SAS exome AF: 0.843

Gnomad4 FIN exome AF: 0.894

Gnomad4 NFE exome AF: 0.867

Gnomad4 OTH exome AF: 0.881

GnomAD4 genome AF: 0.882 AC: 134198 AN: 152170 Hom.: 59240 Cov.: 33 AF XY: 0.881 AC XY: 65505 AN XY: 74378

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.872

Alfa AF: 0.882 Hom.: 7346

Bravo AF: 0.886

Asia WGS AF: 0.884 AC: 3045 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.44

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: rs7595255; hg19: chr2-167082978;