Variant 20-63361854-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NR_110634.1(LOC100130587):n.219C>T 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 0.167 in 152,200 control chromosomes in the GnomAD database, including 2,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2602 hom., cov: 30)

Exomes 𝑓: 0.090 ( 1 hom. )

Consequence

LOC100130587
NR_110634.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.193

Variant links:

Genes affected

(HGNC:):

links:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 20-63361854-C-T is Benign according to our data. Variant chr20-63361854-C-T is described in ClinVar as [Benign]. Clinvar id is 1169561.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC100130587	NR_110634.1 linkuse as main transcript	n.219C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
	ENST00000370257.1 linkuse as main transcript	n.219C>T	non_coding_transcript_exon_variant	2/5	2
CHRNA4	ENST00000463705.5 linkuse as main transcript	n.1032-10827G>A	intron_variant, non_coding_transcript_variant		1
CHRNA4	ENST00000675470.1 linkuse as main transcript	c.-689G>A	5_prime_UTR_variant	3/5

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25399

AN:

151982

Hom.:

2603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.575

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.0900

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.0811

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.667

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0429

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.167

AC:

25411

AN:

152100

Hom.:

2602

Cov.:

AF XY:

0.171

AC XY:

12688

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.575

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.143

Hom.:

249

Bravo

AF:

0.169

Asia WGS

AF:

0.375

AC:

1301

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal dominant nocturnal frontal lobe epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.91

Splicing

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