dbSNP rs41272375: CHRNB3:c.-160G>C (chr8-42697387-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

3 publications found

Variant links:

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]

CHRNB3 links:

LOC124900250 (HGNC:):

LOC124900250 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
CHRNB3	NM_000749.5 link	c.-160G>C	5_prime_UTR_variant	Exon 1 of 6	ENST00000289957.3	NP_000740.1	Q05901
LOC124900250	XR_001745887.2 link	n.194C>G	non_coding_transcript_exon_variant	Exon 2 of 3
CHRNB3	NM_001347717.2 link	c.-515G>C	5_prime_UTR_variant	Exon 1 of 7		NP_001334646.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNB3	ENST00000289957.3 link	c.-160G>C	5_prime_UTR_variant	Exon 1 of 6	1	NM_000749.5	ENSP00000289957.2	Q05901
CHRNB3	ENST00000531610.5 link	n.12G>C	non_coding_transcript_exon_variant	Exon 1 of 4	4
CHRNB3	ENST00000534391.1 link	c.-515G>C	5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000433913.1	A0A1D5RMT8

Frequencies

GnomAD3 genomes

AF:

0.0328

AC:

4986

AN:

152210

Hom.:

211

Cov.:

show subpopulations

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.:

AF XY:

0.0306

AC XY:

7255

AN XY:

237282

show subpopulations

African (AFR)

AF:

0.00660

AC:

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:

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:

AN:

3586

European-Non Finnish (NFE)

AF:

0.0289

AC:

7670

AN:

265376

Other (OTH)

AF:

0.0319

AC:

831

AN:

26030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

633

1267

1900

2534

3167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0328

AC:

4990

AN:

152328

Hom.:

210

Cov.:

AF XY:

0.0347

AC XY:

2584

AN XY:

74482

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0178

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0511

AC:

543

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0288

AC:

1961

AN:

68032

Other (OTH)

AF:

0.0331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

226

453

679

906

1132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0330

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.0110

AC:

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

(source)

DANN

Benign

0.51

PhyloP100

1.8

PromoterAI

-0.00050

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over