NM_000749.5:c.-160G>C

Variant names:

• chr8-42697387-G-C
• rs41272375
• NM_000749.5:c.-160G>C

Variant summary

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

The NM_000749.5(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 NM_000749.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 3 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]

LOC124900250 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHRNB3	NM_000749.5	c.-160G>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000289957.3	NP_000740.1
LOC124900250	XR_001745887.2	n.194C>G		non_coding_transcript_exon_variant	Exon 2 of 3
CHRNB3	NM_001347717.2	c.-515G>C		5_prime_UTR_variant	Exon 1 of 7		NP_001334646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB3	ENST00000289957.3	c.-160G>C		5_prime_UTR_variant	Exon 1 of 6	1	NM_000749.5	ENSP00000289957.2
CHRNB3	ENST00000531610.5	n.12G>C		non_coding_transcript_exon_variant	Exon 1 of 4	4
CHRNB3	ENST00000534391.1	c.-515G>C		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000433913.1

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

African (AFR) AF: 0.00660 AC: 85 AN: 12888

American (AMR) AF: 0.159 AC: 3393 AN: 21348

Ashkenazi Jewish (ASJ) AF: 0.0186 AC: 264 AN: 14156

East Asian (EAS) AF: 0.0000320 AC: 1 AN: 31206

South Asian (SAS) AF: 0.0157 AC: 676 AN: 43080

European-Finnish (FIN) AF: 0.0509 AC: 1639 AN: 32170

Middle Eastern (MID) AF: 0.0117 AC: 42 AN: 3586

European-Non Finnish (NFE) AF: 0.0289 AC: 7670 AN: 265376

Other (OTH) AF: 0.0319 AC: 831 AN: 26030

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

African (AFR) AF: 0.00878 AC: 365 AN: 41582

American (AMR) AF: 0.122 AC: 1866 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4828

European-Finnish (FIN) AF: 0.0511 AC: 543 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0288 AC: 1961 AN: 68032

Other (OTH) AF: 0.0331 AC: 70 AN: 2116

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
PhyloP100		1.8
PromoterAI		-0.00050	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs41272375; hg19: chr8-42552530;