dbSNP rs13280604: CHRNB3:c.53-4274G>A (chr8-42704443-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001347717.2(CHRNB3):c.-209G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,102 control chromosomes in the GnomAD database, including 33,726 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 0.63 ( 33720 hom., cov: 32)

Exomes 𝑓: 0.68 ( 6 hom. )

Consequence

CHRNB3
NM_001347717.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.608

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:

LOC105379396 (HGNC:):

LOC105379396 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNB3	NM_000749.5 link	c.53-4274G>A	intron_variant	Intron 1 of 5	ENST00000289957.3	NP_000740.1	Q05901
CHRNB3	NM_001347717.2 link	c.-209G>A	5_prime_UTR_variant	Exon 2 of 7		NP_001334646.1
LOC105379396	XR_007060900.1 link	n.1733C>T	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNB3	ENST00000289957.3 link	c.53-4274G>A	intron_variant	Intron 1 of 5	1	NM_000749.5	ENSP00000289957.2	Q05901
CHRNB3	ENST00000534391.1 link	c.-209G>A	5_prime_UTR_variant	Exon 2 of 4	3		ENSP00000433913.1	A0A1D5RMT8
CHRNB3	ENST00000531610.5 link	n.434G>A	non_coding_transcript_exon_variant	Exon 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95115

AN:

151956

Hom.:

33711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.707

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.778

Gnomad OTH

AF:

0.657

GnomAD4 exome

AF:

0.679

AC:

AN:

Hom.:

Cov.:

AF XY:

0.591

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AC:

AN:

Gnomad4 NFE exome

AF:

0.667

AC:

AN:

Gnomad4 Remaining exome

AF:

0.750

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.626

AC:

95144

AN:

152074

Hom.:

33720

Cov.:

AF XY:

0.631

AC XY:

46942

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.267

AC:

0.266755

AN:

0.266755

Gnomad4 AMR

AF:

0.708

AC:

0.708028

AN:

0.708028

Gnomad4 ASJ

AF:

0.703

AC:

0.702656

AN:

0.702656

Gnomad4 EAS

AF:

0.806

AC:

0.805835

AN:

0.805835

Gnomad4 SAS

AF:

0.708

AC:

0.708212

AN:

0.708212

Gnomad4 FIN

AF:

0.759

AC:

0.759018

AN:

0.759018

Gnomad4 NFE

AF:

0.778

AC:

0.777755

AN:

0.777755

Gnomad4 OTH

AF:

0.658

AC:

0.658444

AN:

0.658444

Heterozygous variant carriers

1439

2879

4318

5758

7197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.707

Hom.:

70412

Bravo

AF:

0.605

Asia WGS

AF:

0.704

AC:

2447

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.57

DANN

Benign

0.68

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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