Genetic Variant SCN9A:c.901+1627C>T (chr2-166301463-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001365536.1(SCN9A):c.901+1627C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 150,576 control chromosomes in the GnomAD database, including 1,933 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 0.13 ( 1933 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

SCN9A
NM_001365536.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350

Publications

0 publications found

Variant links:

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]

SCN9A links:

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

SCN1A-AS1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN9A	NM_001365536.1	MANE Select	c.901+1627C>T	intron	N/A	NP_001352465.1	Q15858-1
SCN9A	NM_002977.4		c.901+1627C>T	intron	N/A	NP_002968.2	Q15858-3
SCN1A-AS1	NR_110260.1		n.1984G>A	non_coding_transcript_exon	Exon 12 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN9A	ENST00000642356.2	MANE Select	c.901+1627C>T	intron	N/A	ENSP00000495601.1	Q15858-1
SCN9A	ENST00000303354.11	TSL:5	c.901+1627C>T	intron	N/A	ENSP00000304748.7	Q15858-1
SCN9A	ENST00000409672.5	TSL:5	c.901+1627C>T	intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20129

AN:

150462

Hom.:

1933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.0967

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.119

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.134

AC:

20133

AN:

150576

Hom.:

1933

Cov.:

AF XY:

0.137

AC XY:

10098

AN XY:

73604

show subpopulations

African (AFR)

AF:

0.141

AC:

5647

AN:

40040

American (AMR)

AF:

0.0968

AC:

1474

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3468

East Asian (EAS)

AF:

0.326

AC:

1685

AN:

5164

South Asian (SAS)

AF:

0.190

AC:

914

AN:

4818

European-Finnish (FIN)

AF:

0.175

AC:

1845

AN:

10570

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7782

AN:

67986

Other (OTH)

AF:

0.122

AC:

256

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

832

1665

2497

3330

4162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

167

Bravo

AF:

0.130

Asia WGS

AF:

0.236

AC:

818

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

4.4

(source)

DANN

Benign

0.52

PhyloP100

0.035

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over