rs41272375

Positions:

• chr8-42697387-G-C

Variant summary

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

The ENST00000289957.3(CHRNB3):​c.-160G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 602,168 control chromosomes in the GnomAD database, including 679 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 0.033 (210 hom., cov: 32)
  • Exomes 𝑓: 0.032 (469 hom.)
• Consequence: CHRNB3 ENST00000289957.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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]

LOC124900250 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB3	NM_000749.5	c.-160G>C		5_prime_UTR_variant	1/6	ENST00000289957.3	NP_000740.1
LOC124900250	XR_001745887.2	n.194C>G		non_coding_transcript_exon_variant	2/3
CHRNB3	NM_001347717.2	c.-515G>C		5_prime_UTR_variant	1/7		NP_001334646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957.3	c.-160G>C		5_prime_UTR_variant	1/6	1	NM_000749.5	ENSP00000289957	P1
CHRNB3	ENST00000534391.1	c.-515G>C		5_prime_UTR_variant	1/4	3		ENSP00000433913
CHRNB3	ENST00000531610.5	n.12G>C		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4986 AN: 152210 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.00878

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0334

GnomAD4 exome AF: 0.0325 AC: 14601 AN: 449840 Hom.: 469 Cov.: 5 AF XY: 0.0306 AC XY: 7255 AN XY: 237282

Gnomad4 AFR exome AF: 0.00660

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.0186

Gnomad4 EAS exome AF: 0.0000320

Gnomad4 SAS exome AF: 0.0157

Gnomad4 FIN exome AF: 0.0509

Gnomad4 NFE exome AF: 0.0289

Gnomad4 OTH exome AF: 0.0319

GnomAD4 genome AF: 0.0328 AC: 4990 AN: 152328 Hom.: 210 Cov.: 32 AF XY: 0.0347 AC XY: 2584 AN XY: 74482

Gnomad4 AFR AF: 0.00878

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0330 Hom.: 18

Bravo AF: 0.0375

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41272375; hg19: chr8-42552530;