chr8-42719453-C-T

Variant names:

• chr8-42719453-C-T
• rs11783289
• NM_000749.5:c.249+9019C>T

Variant summary

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

The NM_000749.5(CHRNB3):​c.249+9019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,062 control chromosomes in the GnomAD database, including 46,091 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 0.76 (46091 hom., cov: 32)
• Consequence: CHRNB3 NM_000749.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 5 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]

ENSG00000255101 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000749.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB3	NM_000749.5	MANE Select	c.249+9019C>T		intron	N/A	NP_000740.1
	CHRNB3	NM_001347717.2		c.27+9019C>T		intron	N/A	NP_001334646.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB3	ENST00000289957.3	TSL:1 MANE Select	c.249+9019C>T		intron	N/A	ENSP00000289957.2
	ENSG00000255101	ENST00000527318.1	TSL:4	n.145+2349G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116090 AN: 151942 Hom.: 46076 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.764 AC: 116150 AN: 152062 Hom.: 46091 Cov.: 32 AF XY: 0.771 AC XY: 57315 AN XY: 74336

African (AFR) AF: 0.534 AC: 22096 AN: 41372

American (AMR) AF: 0.779 AC: 11906 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2908 AN: 3472

East Asian (EAS) AF: 0.869 AC: 4502 AN: 5178

South Asian (SAS) AF: 0.873 AC: 4206 AN: 4820

European-Finnish (FIN) AF: 0.894 AC: 9489 AN: 10614

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58364 AN: 68018

Other (OTH) AF: 0.759 AC: 1599 AN: 2106

Alfa AF: 0.815 Hom.: 7020

Bravo AF: 0.741

Asia WGS AF: 0.816 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.34
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: rs11783289; hg19: chr8-42574596;