rs13280604

Positions:

• chr8-42704443-G-A

Variant summary

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

The NM_000749.5(CHRNB3):​c.53-4274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,102 control chromosomes in the GnomAD database, including 33,726 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 0.63 (33720 hom., cov: 32)
  • Exomes 𝑓: 0.68 (6 hom.)
• Consequence: CHRNB3 NM_000749.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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]

LOC105379396 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB3	NM_000749.5	c.53-4274G>A		intron_variant		ENST00000289957.3	NP_000740.1
LOC105379396	XR_007060900.1	n.1733C>T		non_coding_transcript_exon_variant	2/2
CHRNB3	NM_001347717.2	c.-209G>A		5_prime_UTR_variant	2/7		NP_001334646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957.3	c.53-4274G>A		intron_variant		1	NM_000749.5	ENSP00000289957	P1
CHRNB3	ENST00000534391.1	c.-209G>A		5_prime_UTR_variant	2/4	3		ENSP00000433913
CHRNB3	ENST00000531610.5	n.434G>A		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95115 AN: 151956 Hom.: 33711 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.679 AC: 19 AN: 28 Hom.: 6 Cov.: 0 AF XY: 0.591 AC XY: 13 AN XY: 22

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.626 AC: 95144 AN: 152074 Hom.: 33720 Cov.: 32 AF XY: 0.631 AC XY: 46942 AN XY: 74346

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.658

Alfa AF: 0.705 Hom.: 13852

Bravo AF: 0.605

Asia WGS AF: 0.704 AC: 2447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs13280604; hg19: chr8-42559586;