Variant chr20-63359526-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 ENST00000370263.9(CHRNA4):c.228+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,612,242 control chromosomes in the GnomAD database, including 5,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 744 hom., cov: 34)

Exomes 𝑓: 0.077 ( 5140 hom. )

Consequence

CHRNA4
ENST00000370263.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.30

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=-1.0).

BP6

Variant 20-63359526-C-T is Benign according to our data. Variant chr20-63359526-C-T is described in ClinVar as [Benign]. Clinvar id is 1251570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63359526-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CHRNA4	NM_000744.7 linkuse as main transcript	c.228+22G>A	intron_variant	ENST00000370263.9	NP_000735.1
CHRNA4	NM_001256573.2 linkuse as main transcript	c.-319+22G>A	intron_variant		NP_001243502.1
CHRNA4	NR_046317.2 linkuse as main transcript	n.412+22G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA4	ENST00000370263.9 linkuse as main transcript	c.228+22G>A		intron_variant		1	NM_000744.7	ENSP00000359285	P1	P43681-1

Frequencies

GnomAD3 genomes

AF:

0.0955

AC:

14534

AN:

152138

Hom.:

743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.0765

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0870

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0713

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0918

AC:

22896

AN:

249412

Hom.:

1233

AF XY:

0.0948

AC XY:

12841

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0479

Gnomad ASJ exome

AF:

0.0964

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.0886

Gnomad NFE exome

AF:

0.0746

Gnomad OTH exome

AF:

0.0909

GnomAD4 exome

AF:

0.0774

AC:

112965

AN:

1459986

Hom.:

5140

Cov.:

AF XY:

0.0797

AC XY:

57902

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.0512

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.0869

Gnomad4 NFE exome

AF:

0.0668

Gnomad4 OTH exome

AF:

0.0845

GnomAD4 genome

AF:

0.0956

AC:

14556

AN:

152256

Hom.:

744

Cov.:

AF XY:

0.0965

AC XY:

7183

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.0765

Gnomad4 ASJ

AF:

0.0888

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.0870

Gnomad4 NFE

AF:

0.0713

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0836

Hom.:

121

Bravo

AF:

0.0941

Asia WGS

AF:

0.143

AC:

496

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 22% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.18

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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