Variant rs2273500 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000744.7(CHRNA4):c.383+378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,305,208 control chromosomes in the GnomAD database, including 17,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2035 hom., cov: 32)

Exomes 𝑓: 0.16 ( 15129 hom. )

Consequence

CHRNA4
NM_000744.7 intron

Scores

Splicing: ADA: 0.00006553

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.67

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:

CHRNA4 (HGNC:):

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_addAF=-0.955197).

BP6

Variant 20-63355597-T-C is Benign according to our data. Variant chr20-63355597-T-C is described in ClinVar as [Benign]. Clinvar id is 3255299.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63355597-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CHRNA4	NM_000744.7 linkuse as main transcript	c.383+378A>G	intron_variant	ENST00000370263.9	NP_000735.1	P43681-1B4DK78Q59FV0
CHRNA4	NM_001256573.2 linkuse as main transcript	c.-146+360A>G	intron_variant		NP_001243502.1	P43681Q4VAQ3B4DK78Q59FV0
CHRNA4	NR_046317.2 linkuse as main transcript	n.592+378A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA4	ENST00000370263.9 linkuse as main transcript	c.383+378A>G		intron_variant		1	NM_000744.7	ENSP00000359285.4		P43681-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24284

AN:

152010

Hom.:

2032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.164

AC:

22355

AN:

136100

Hom.:

2096

AF XY:

0.175

AC XY:

12933

AN XY:

74082

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0818

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.156

AC:

179348

AN:

1153080

Hom.:

15129

Cov.:

AF XY:

0.160

AC XY:

90597

AN XY:

565876

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0835

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.285

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.160

AC:

24312

AN:

152128

Hom.:

2035

Cov.:

AF XY:

0.164

AC XY:

12190

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.147

Hom.:

555

Bravo

AF:

0.147

TwinsUK

AF:

0.141

AC:

522

ALSPAC

AF:

0.144

AC:

556

ExAC

AF:

0.163

AC:

3506

Asia WGS

AF:

0.214

AC:

746

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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 29% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.96

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.2

DANN

Benign

0.49

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00039

GERP RS

-0.045

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000066

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.010

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