8-42737160-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHRNB3	NM_000749.5	c.*542T>C		3_prime_UTR_variant	6/6	ENST00000289957.3
CHRNB3	NM_001347717.2	c.*542T>C		3_prime_UTR_variant	7/7
CHRNB3	XM_011544390.3	c.*542T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB3	ENST00000289957.3	c.*542T>C		3_prime_UTR_variant	6/6	1	NM_000749.5	P1

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.987

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.964

Gnomad4 OTH exome AF: 0.971

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

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.967

Gnomad4 OTH AF: 0.975

Alfa AF: 0.971 Hom.: 39608

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

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

Other links and lift over

dbSNP: rs7012713; hg19: chr8-42592303;