rs11636753

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000750.5(CHRNB4):​c.56-1017C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 149,836 control chromosomes in the GnomAD database, including 9,210 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 0.35 ( 9210 hom., cov: 30)

Consequence

CHRNB4
NM_000750.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33
Variant links:
Genes affected
CHRNB4 (HGNC:1964): (cholinergic receptor nicotinic beta 4 subunit) This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHRNB4NM_000750.5 linkuse as main transcriptc.56-1017C>A intron_variant ENST00000261751.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRNB4ENST00000261751.8 linkuse as main transcriptc.56-1017C>A intron_variant 1 NM_000750.5 P1P30926-1
CHRNB4ENST00000412074.6 linkuse as main transcriptc.56-1017C>A intron_variant 1 P30926-2
CHRNB4ENST00000559849.5 linkuse as main transcriptc.47-1017C>A intron_variant, NMD_transcript_variant 1
CHRNB4ENST00000560511.5 linkuse as main transcriptn.410-1017C>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.348
AC:
52045
AN:
149746
Hom.:
9208
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.310
Gnomad AMI
AF:
0.428
Gnomad AMR
AF:
0.246
Gnomad ASJ
AF:
0.387
Gnomad EAS
AF:
0.184
Gnomad SAS
AF:
0.298
Gnomad FIN
AF:
0.350
Gnomad MID
AF:
0.277
Gnomad NFE
AF:
0.406
Gnomad OTH
AF:
0.330
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.347
AC:
52067
AN:
149836
Hom.:
9210
Cov.:
30
AF XY:
0.342
AC XY:
24993
AN XY:
72980
show subpopulations
Gnomad4 AFR
AF:
0.310
Gnomad4 AMR
AF:
0.245
Gnomad4 ASJ
AF:
0.387
Gnomad4 EAS
AF:
0.183
Gnomad4 SAS
AF:
0.297
Gnomad4 FIN
AF:
0.350
Gnomad4 NFE
AF:
0.406
Gnomad4 OTH
AF:
0.328
Alfa
AF:
0.370
Hom.:
7140
Bravo
AF:
0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.34
DANN
Benign
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11636753; hg19: chr15-78928946; API