rs13280604

Variant names:

• chr8-42704443-G-A
• rs13280604
• NM_000749.5:c.53-4274G>A

Variant summary

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

The NM_001347717.2(CHRNB3):​c.-209G>A variant causes a 5 prime UTR 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_001347717.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 42 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]

LOC105379396 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347717.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB3	NM_000749.5	MANE Select	c.53-4274G>A		intron	N/A	NP_000740.1	Q05901
	CHRNB3	NM_001347717.2		c.-209G>A		5_prime_UTR	Exon 2 of 7	NP_001334646.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB3	ENST00000289957.3	TSL:1 MANE Select	c.53-4274G>A		intron	N/A	ENSP00000289957.2	Q05901
	CHRNB3	ENST00000534391.1	TSL:3	c.-209G>A		5_prime_UTR	Exon 2 of 4	ENSP00000433913.1	A0A1D5RMT8
	CHRNB3	ENST00000531610.5	TSL:4	n.434G>A		non_coding_transcript_exon	Exon 3 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 16 AN: 24

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.267 AC: 11057 AN: 41450

American (AMR) AF: 0.708 AC: 10813 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2434 AN: 3464

East Asian (EAS) AF: 0.806 AC: 4171 AN: 5176

South Asian (SAS) AF: 0.708 AC: 3415 AN: 4822

European-Finnish (FIN) AF: 0.759 AC: 8038 AN: 10590

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52878 AN: 67988

Other (OTH) AF: 0.658 AC: 1388 AN: 2108

Alfa AF: 0.707 Hom.: 70412

Bravo AF: 0.605

Asia WGS AF: 0.704 AC: 2447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.68
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13280604; hg19: chr8-42559586;