dbSNP rs4447616: SCN9A:c.259-79G>A (chr2-166307153-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001365536.1(SCN9A):c.259-79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 786,280 control chromosomes in the GnomAD database, including 160,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.67 ( 35589 hom., cov: 31)

Exomes 𝑓: 0.62 ( 125278 hom. )

Consequence

SCN9A
NM_001365536.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.22

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-166307153-C-T is Benign according to our data. Variant chr2-166307153-C-T is described in ClinVar as Benign. ClinVar VariationId is 3255239.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 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.259-79G>A		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.259-79G>A		intron	N/A	NP_002968.2	Q15858-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN9A	ENST00000642356.2	MANE Select	c.259-79G>A	intron	N/A	ENSP00000495601.1	Q15858-1
SCN9A	ENST00000303354.11	TSL:5	c.259-79G>A	intron	N/A	ENSP00000304748.7	Q15858-1
SCN9A	ENST00000409672.5	TSL:5	c.259-79G>A	intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102389

AN:

151864

Hom.:

35550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.834

Gnomad AMI

AF:

0.740

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.546

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.648

Gnomad OTH

AF:

0.668

GnomAD4 exome

AF:

0.623

AC:

395351

AN:

634300

Hom.:

125278

AF XY:

0.620

AC XY:

208391

AN XY:

336060

show subpopulations

African (AFR)

AF:

0.832

AC:

13782

AN:

16574

American (AMR)

AF:

0.480

AC:

14971

AN:

31172

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

9657

AN:

18268

East Asian (EAS)

AF:

0.463

AC:

14913

AN:

32228

South Asian (SAS)

AF:

0.552

AC:

31379

AN:

56850

European-Finnish (FIN)

AF:

0.602

AC:

28396

AN:

47152

Middle Eastern (MID)

AF:

0.562

AC:

1715

AN:

3052

European-Non Finnish (NFE)

AF:

0.656

AC:

260334

AN:

396942

Other (OTH)

AF:

0.630

AC:

20204

AN:

32062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6834

13668

20501

27335

34169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3184

6368

9552

12736

15920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.674

AC:

102473

AN:

151980

Hom.:

35589

Cov.:

AF XY:

0.666

AC XY:

49465

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.834

AC:

34601

AN:

41506

American (AMR)

AF:

0.568

AC:

8669

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

1804

AN:

3464

East Asian (EAS)

AF:

0.430

AC:

2211

AN:

5146

South Asian (SAS)

AF:

0.546

AC:

2634

AN:

4822

European-Finnish (FIN)

AF:

0.600

AC:

6329

AN:

10542

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.648

AC:

43989

AN:

67916

Other (OTH)

AF:

0.663

AC:

1399

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1640

3281

4921

6562

8202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.655

Hom.:

13044

Bravo

AF:

0.675

Asia WGS

AF:

0.511

AC:

1779

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.6

(source)

DANN

Benign

0.74

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over