Variant 20-63356470-C-T 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.229-55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,528,598 control chromosomes in the GnomAD database, including 5,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 753 hom., cov: 31)

Exomes 𝑓: 0.078 ( 4977 hom. )

Consequence

CHRNA4
NM_000744.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.892

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:

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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 20-63356470-C-T is Benign according to our data. Variant chr20-63356470-C-T is described in ClinVar as [Benign]. Clinvar id is 1238055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63356470-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CHRNA4	NM_000744.7 linkuse as main transcript	c.229-55G>A	intron_variant	ENST00000370263.9
CHRNA4	NM_001256573.2 linkuse as main transcript	c.-318-55G>A	intron_variant
CHRNA4	NR_046317.2 linkuse as main transcript	n.413-55G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA4	ENST00000370263.9 linkuse as main transcript	c.229-55G>A		intron_variant		1	NM_000744.7	P1	P43681-1

Frequencies

GnomAD3 genomes

AF:

0.0962

AC:

14600

AN:

151792

Hom.:

751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.0885

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.0873

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0713

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.0781

AC:

107574

AN:

1376688

Hom.:

4977

Cov.:

AF XY:

0.0805

AC XY:

54932

AN XY:

682258

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.0543

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.0877

Gnomad4 NFE exome

AF:

0.0671

Gnomad4 OTH exome

AF:

0.0859

GnomAD4 genome

AF:

0.0963

AC:

14625

AN:

151910

Hom.:

753

Cov.:

AF XY:

0.0972

AC XY:

7220

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0766

Gnomad4 ASJ

AF:

0.0885

Gnomad4 EAS

AF:

0.130

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.0873

Gnomad4 NFE

AF:

0.0713

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0838

Hom.:

159

Bravo

AF:

0.0949

Asia WGS

AF:

0.148

AC:

512

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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