rs7838246

Variant names:

• chr8-42730154-A-G
• rs7838246
• NM_000749.5:c.250-440A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.97).
• 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 rank	MANE	Protein	UniProt
CHRNB3	NM_000749.5	c.250-440A>G		intron_variant	Intron 3 of 5	ENST00000289957.3	NP_000740.1
CHRNB3	NM_001347717.2	c.28-440A>G		intron_variant	Intron 4 of 6		NP_001334646.1
CHRNB3	XM_011544390.3	c.-138-440A>G		intron_variant	Intron 1 of 3		XP_011542692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957.3	c.250-440A>G		intron_variant	Intron 3 of 5	1	NM_000749.5	ENSP00000289957.2

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

African (AFR) AF: 0.0973 AC: 4040 AN: 41510

American (AMR) AF: 0.0387 AC: 592 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3468

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5196

South Asian (SAS) AF: 0.0802 AC: 387 AN: 4828

European-Finnish (FIN) AF: 0.0500 AC: 530 AN: 10608

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0384 AC: 2614 AN: 68032

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0488 Hom.: 37

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
PhyloP100		-0.43
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: rs7838246; hg19: chr8-42585297;