8-42737160-T-C

Variant names:

• chr8-42737160-T-C
• rs7012713
• NM_000749.5:c.*542T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000749.5(CHRNB3):​c.*542T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 153,076 control chromosomes in the GnomAD database, including 73,437 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 0.98 (72994 hom., cov: 29)
  • Exomes 𝑓: 0.97 (443 hom.)
• Consequence: CHRNB3 NM_000749.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 14 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB3	NM_000749.5	c.*542T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000289957.3	NP_000740.1
CHRNB3	NM_001347717.2	c.*542T>C		3_prime_UTR_variant	Exon 7 of 7		NP_001334646.1
CHRNB3	XM_011544390.3	c.*542T>C		3_prime_UTR_variant	Exon 4 of 4		XP_011542692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957.3	c.*542T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_000749.5	ENSP00000289957.2

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148886 AN: 152020 Hom.: 72933 Cov.: 29

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.975

GnomAD4 exome AF: 0.971 AC: 911 AN: 938 Hom.: 443 Cov.: 0 AF XY: 0.969 AC XY: 494 AN XY: 510

African (AFR) AF: 1.00 AC: 12 AN: 12

American (AMR) AF: 0.987 AC: 150 AN: 152

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 1.00 AC: 8 AN: 8

South Asian (SAS) AF: 1.00 AC: 36 AN: 36

European-Finnish (FIN) AF: 1.00 AC: 16 AN: 16

Middle Eastern (MID) AF: 1.00 AC: 6 AN: 6

European-Non Finnish (NFE) AF: 0.964 AC: 646 AN: 670

Other (OTH) AF: 0.971 AC: 33 AN: 34

GnomAD4 genome AF: 0.979 AC: 149005 AN: 152138 Hom.: 72994 Cov.: 29 AF XY: 0.980 AC XY: 72872 AN XY: 74342

African (AFR) AF: 0.994 AC: 41259 AN: 41522

American (AMR) AF: 0.980 AC: 14972 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3386 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5150 AN: 5150

South Asian (SAS) AF: 0.999 AC: 4802 AN: 4806

European-Finnish (FIN) AF: 0.980 AC: 10387 AN: 10594

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65788 AN: 68002

Other (OTH) AF: 0.975 AC: 2061 AN: 2114

Alfa AF: 0.971 Hom.: 57262

Bravo AF: 0.979

Asia WGS AF: 0.997 AC: 3469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.1
DANN	Benign	0.43
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7012713; hg19: chr8-42592303;