chr2-166226468-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.4398+99A>G		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.4365+99A>G		intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.612-21727T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.4398+99A>G		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.4398+99A>G		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.4365+99A>G		intron	N/A	ENSP00000386306.1	Q15858-3

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

African (AFR) AF: 0.909 AC: 13557 AN: 14914

American (AMR) AF: 0.897 AC: 14898 AN: 16600

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 13624 AN: 14982

East Asian (EAS) AF: 0.951 AC: 27883 AN: 29334

South Asian (SAS) AF: 0.843 AC: 31236 AN: 37036

European-Finnish (FIN) AF: 0.894 AC: 38279 AN: 42794

Middle Eastern (MID) AF: 0.879 AC: 2041 AN: 2322

European-Non Finnish (NFE) AF: 0.867 AC: 387618 AN: 447082

Other (OTH) AF: 0.881 AC: 27349 AN: 31038

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

African (AFR) AF: 0.907 AC: 37685 AN: 41554

American (AMR) AF: 0.883 AC: 13490 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3160 AN: 3472

East Asian (EAS) AF: 0.950 AC: 4930 AN: 5190

South Asian (SAS) AF: 0.829 AC: 4003 AN: 4828

European-Finnish (FIN) AF: 0.887 AC: 9400 AN: 10596

Middle Eastern (MID) AF: 0.884 AC: 258 AN: 292

European-Non Finnish (NFE) AF: 0.863 AC: 58641 AN: 67940

Other (OTH) AF: 0.872 AC: 1842 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.44
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7595255; hg19: chr2-167082978;