Variant rs4447616 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 3255239.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-166307153-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN9A	NM_001365536.1 linkuse as main transcript	c.259-79G>A		intron_variant		ENST00000642356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN9A	ENST00000642356.2 linkuse as main transcript	c.259-79G>A		intron_variant			NM_001365536.1	P1	Q15858-1
SCN1A-AS1	ENST00000651574.1 linkuse as main transcript	n.1977+11024C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome

AF:

0.832

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.529

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.552

Gnomad4 FIN exome

AF:

0.602

Gnomad4 NFE exome

AF:

0.656

Gnomad4 OTH exome

AF:

0.630

GnomAD4 genome

AF:

0.674

AC:

102473

AN:

151980

Hom.:

35589

Cov.:

AF XY:

0.666

AC XY:

49465

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.834

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.521

Gnomad4 EAS

AF:

0.430

Gnomad4 SAS

AF:

0.546

Gnomad4 FIN

AF:

0.600

Gnomad4 NFE

AF:

0.648

Gnomad4 OTH

AF:

0.663

Alfa

AF:

0.655

Hom.:

8500

Bravo

AF:

0.675

Asia WGS

AF:

0.511

AC:

1779

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 76% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 71. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.6

DANN

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over