chr8-42730154-A-G

Position:

• chr8-42730154-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000749.5(CHRNB3):​c.250-440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 152,250 control chromosomes in the GnomAD database, including 328 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 0.057 (328 hom., cov: 32)
• Consequence: CHRNB3 NM_000749.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB3	NM_000749.5	c.250-440A>G		intron_variant		ENST00000289957.3
CHRNB3	NM_001347717.2	c.28-440A>G		intron_variant
CHRNB3	XM_011544390.3	c.-138-440A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB3	ENST00000289957.3	c.250-440A>G		intron_variant		1	NM_000749.5	P1

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8739 AN: 152132 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.0803

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0384

Gnomad OTH AF: 0.0525

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

GnomAD4 genome AF: 0.0574 AC: 8745 AN: 152250 Hom.: 328 Cov.: 32 AF XY: 0.0567 AC XY: 4218 AN XY: 74438

Gnomad4 AFR AF: 0.0973

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0802

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0384

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0470 Hom.: 31

Bravo AF: 0.0589

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.63

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: rs7838246; hg19: chr8-42585297;