Variant rs2236196 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000744.7(CHRNA4):c.*534C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 454,030 control chromosomes in the GnomAD database, including 109,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 32183 hom., cov: 33)

Exomes 𝑓: 0.71 ( 76932 hom. )

Consequence

CHRNA4
NM_000744.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.150

Variant links:

Genes affected

CHRNA4 (HGNC:1958): (cholinergic receptor nicotinic alpha 4 subunit) This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

CHRNA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 20-63346204-G-A is Benign according to our data. Variant chr20-63346204-G-A is described in ClinVar as [Benign]. Clinvar id is 1169560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CHRNA4	NM_000744.7 linkuse as main transcript	c.*534C>T	3_prime_UTR_variant	6/6	ENST00000370263.9	NP_000735.1
CHRNA4	NM_001256573.2 linkuse as main transcript	c.*534C>T	3_prime_UTR_variant	6/6		NP_001243502.1
CHRNA4	NR_046317.2 linkuse as main transcript	n.2627C>T	non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA4	ENST00000370263.9 linkuse as main transcript	c.*534C>T	3_prime_UTR_variant	6/6	1	NM_000744.7	ENSP00000359285	P1	P43681-1
CHRNA4	ENST00000463705.5 linkuse as main transcript	n.3066C>T	non_coding_transcript_exon_variant	5/5	1
CHRNA4	ENST00000631289.1 linkuse as main transcript	n.732C>T	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95517

AN:

152014

Hom.:

32173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.638

Gnomad AMR

AF:

0.729

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.860

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.737

Gnomad OTH

AF:

0.626

GnomAD3 exomes

AF:

0.713

AC:

92972

AN:

130384

Hom.:

34078

AF XY:

0.705

AC XY:

50135

AN XY:

71156

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.826

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.860

Gnomad SAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.734

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.707

AC:

213307

AN:

301898

Hom.:

76932

Cov.:

AF XY:

0.699

AC XY:

120231

AN XY:

172048

show subpopulations

Gnomad4 AFR exome

AF:

0.351

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.862

Gnomad4 SAS exome

AF:

0.617

Gnomad4 FIN exome

AF:

0.728

Gnomad4 NFE exome

AF:

0.739

Gnomad4 OTH exome

AF:

0.687

GnomAD4 genome

AF:

0.628

AC:

95561

AN:

152132

Hom.:

32183

Cov.:

AF XY:

0.633

AC XY:

47038

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.729

Gnomad4 ASJ

AF:

0.599

Gnomad4 EAS

AF:

0.860

Gnomad4 SAS

AF:

0.600

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.737

Gnomad4 OTH

AF:

0.631

Alfa

AF:

0.705

Hom.:

24926

Bravo

AF:

0.620

Asia WGS

AF:

0.720

AC:

2504

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant nocturnal frontal lobe epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Autosomal dominant nocturnal frontal lobe epilepsy 1;C1861063:Tobacco addiction, susceptibility to

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 03, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.93

DANN

Benign

0.53

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

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