Variant 8-42697490-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000749.5(CHRNB3):c.-57G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,486,606 control chromosomes in the GnomAD database, including 419,730 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 33682 hom., cov: 31)

Exomes 𝑓: 0.76 ( 386048 hom. )

Consequence

CHRNB3
NM_000749.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.266

Variant links:

Genes affected

CHRNB3 (HGNC:1963): (cholinergic receptor nicotinic beta 3 subunit) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are (hetero)pentamers composed of homologous subunits. The subunits that make up the muscle and neuronal forms of nAChRs are encoded by separate genes and have different primary structure. There are several subtypes of neuronal nAChRs that vary based on which homologous subunits are arranged around the central channel. They are classified as alpha-subunits if, like muscle alpha-1 (MIM 100690), they have a pair of adjacent cysteines as part of the presumed acetylcholine binding site. Subunits lacking these cysteine residues are classified as beta-subunits (Groot Kormelink and Luyten, 1997 [PubMed 9009220]). Elliott et al. (1996) [PubMed 8906617] stated that the proposed structure for each subunit is a conserved N-terminal extracellular domain followed by 3 conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.[supplied by OMIM, Apr 2010]

CHRNB3 links:

LOC124900250 (HGNC:):

LOC124900250 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB3	NM_000749.5 link	c.-57G>A		5_prime_UTR_premature_start_codon_gain_variant	1/6	ENST00000289957.3	NP_000740.1	Q05901
CHRNB3	NM_000749.5 link	c.-57G>A		5_prime_UTR_variant	1/6	ENST00000289957.3	NP_000740.1	Q05901

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957 link	c.-57G>A		5_prime_UTR_premature_start_codon_gain_variant	1/6	1	NM_000749.5	ENSP00000289957.2		Q05901
CHRNB3	ENST00000289957 link	c.-57G>A		5_prime_UTR_variant	1/6	1	NM_000749.5	ENSP00000289957.2		Q05901

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94994

AN:

151918

Hom.:

33675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.710

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.778

Gnomad OTH

AF:

0.656

GnomAD4 exome

AF:

0.756

AC:

1008274

AN:

1334568

Hom.:

386048

Cov.:

AF XY:

0.754

AC XY:

504517

AN XY:

668712

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.744

Gnomad4 ASJ exome

AF:

0.708

Gnomad4 EAS exome

AF:

0.839

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.762

Gnomad4 NFE exome

AF:

0.776

Gnomad4 OTH exome

AF:

0.727

GnomAD4 genome

AF:

0.625

AC:

95020

AN:

152038

Hom.:

33682

Cov.:

AF XY:

0.631

AC XY:

46897

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.707

Gnomad4 ASJ

AF:

0.704

Gnomad4 EAS

AF:

0.806

Gnomad4 SAS

AF:

0.711

Gnomad4 FIN

AF:

0.760

Gnomad4 NFE

AF:

0.778

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.739

Hom.:

42171

Bravo

AF:

0.604

Asia WGS

AF:

0.705

AC:

2449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.61

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over