ENST00000447809.2:n.2297C>A

Variant names:

• chr2-166301776-C-A
• rs12620053
• ENST00000447809.2:n.2297C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000447809.2(SCN1A-AS1):​n.2297C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 150,228 control chromosomes in the GnomAD database, including 27,816 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 0.60 (27816 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SCN1A-AS1 ENST00000447809.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 8 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• primary erythermalgia

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P
• generalized epilepsy with febrile seizures plus, type 7

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• paroxysmal extreme pain disorder

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• channelopathy-associated congenital insensitivity to pain, autosomal recessive

  Inheritance: SD, AD, AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• sodium channelopathy-related small fiber neuropathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Illumina, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.901+1314G>T		intron_variant	Intron 7 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.901+1314G>T		intron_variant	Intron 7 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.901+1314G>T		intron_variant	Intron 7 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.901+1314G>T		intron_variant	Intron 7 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.901+1314G>T		intron_variant	Intron 7 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.901+1314G>T		intron_variant	Intron 7 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.901+1314G>T		intron_variant	Intron 8 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 89773 AN: 150116 Hom.: 27792 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.579

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.598 AC: 89837 AN: 150228 Hom.: 27816 Cov.: 31 AF XY: 0.599 AC XY: 43944 AN XY: 73416

African (AFR) AF: 0.665 AC: 26466 AN: 39820

American (AMR) AF: 0.585 AC: 8912 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3149 AN: 5158

South Asian (SAS) AF: 0.556 AC: 2678 AN: 4818

European-Finnish (FIN) AF: 0.621 AC: 6543 AN: 10530

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38290 AN: 67922

Other (OTH) AF: 0.581 AC: 1214 AN: 2088

Alfa AF: 0.621 Hom.: 7093

Bravo AF: 0.600

Asia WGS AF: 0.605 AC: 2080 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.9
DANN	Benign	0.85
PhyloP100		0.22
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: rs12620053; hg19: chr2-167158286;