Variant rs6090387 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.-30C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,453,094 control chromosomes in the GnomAD database, including 407,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 35383 hom., cov: 26)

Exomes 𝑓: 0.75 ( 372235 hom. )

Consequence

CHRNA4
NM_000744.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.228

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_noAF=-0.77).

BP6

Variant 20-63361195-G-C is Benign according to our data. Variant chr20-63361195-G-C is described in ClinVar as [Benign]. Clinvar id is 3255233.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63361195-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA4	NM_000744.7 linkuse as main transcript	c.-30C>G	5_prime_UTR_variant	1/6	ENST00000370263.9	NP_000735.1	P43681-1B4DK78Q59FV0
CHRNA4	NM_001256573.2 linkuse as main transcript	c.-489C>G	5_prime_UTR_variant	1/6		NP_001243502.1	P43681Q4VAQ3B4DK78Q59FV0
CHRNA4	NR_046317.2 linkuse as main transcript	n.155C>G	non_coding_transcript_exon_variant	1/6
LOC100130587	NR_110634.1 linkuse as main transcript	n.183-623G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA4	ENST00000370263.9 linkuse as main transcript	c.-30C>G		5_prime_UTR_variant	1/6	1	NM_000744.7	ENSP00000359285.4		P43681-1

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

101428

AN:

149920

Hom.:

35357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.740

Gnomad AMR

AF:

0.747

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.699

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.772

Gnomad OTH

AF:

0.661

GnomAD3 exomes

AF:

0.707

AC:

52306

AN:

73954

Hom.:

18965

AF XY:

0.698

AC XY:

29829

AN XY:

42718

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.772

Gnomad ASJ exome

AF:

0.730

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.601

Gnomad FIN exome

AF:

0.705

Gnomad NFE exome

AF:

0.770

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.751

AC:

979257

AN:

1303076

Hom.:

372235

Cov.:

AF XY:

0.748

AC XY:

478862

AN XY:

640390

show subpopulations

Gnomad4 AFR exome

AF:

0.511

Gnomad4 AMR exome

AF:

0.766

Gnomad4 ASJ exome

AF:

0.722

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.599

Gnomad4 FIN exome

AF:

0.713

Gnomad4 NFE exome

AF:

0.780

Gnomad4 OTH exome

AF:

0.724

GnomAD4 genome

AF:

0.677

AC:

101490

AN:

150018

Hom.:

35383

Cov.:

AF XY:

0.674

AC XY:

49337

AN XY:

73218

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.747

Gnomad4 ASJ

AF:

0.738

Gnomad4 EAS

AF:

0.417

Gnomad4 SAS

AF:

0.582

Gnomad4 FIN

AF:

0.699

Gnomad4 NFE

AF:

0.772

Gnomad4 OTH

AF:

0.665

Alfa

AF:

0.649

Hom.:

2154

Bravo

AF:

0.672

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 87% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 81. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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