XM_011521186.3:c.-597G>A

Variant names:

• chr15-78660789-C-T
• rs4887075
• XM_011521186.3:c.-597G>A

Variant summary

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

The XM_011521186.3(CHRNB4):​c.-597G>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 0.898 in 233,418 control chromosomes in the GnomAD database, including 94,295 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 0.89 (60703 hom., cov: 32)
  • Exomes 𝑓: 0.91 (33592 hom.)
• Consequence: CHRNB4 XM_011521186.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 2 publications found

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]

CHRNB4 Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000290426 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000569846.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290426	ENST00000569846.2	TSL:4	n.146C>T		non_coding_transcript_exon	Exon 1 of 6
	CHRNB4	ENST00000560511.5	TSL:3	n.229-5126G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135680 AN: 152130 Hom.: 60677 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.896

GnomAD4 exome AF: 0.908 AC: 73738 AN: 81168 Hom.: 33592 Cov.: 0 AF XY: 0.911 AC XY: 38504 AN XY: 42266

African (AFR) AF: 0.836 AC: 2236 AN: 2676

American (AMR) AF: 0.922 AC: 4182 AN: 4538

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 1759 AN: 1904

East Asian (EAS) AF: 0.799 AC: 2919 AN: 3652

South Asian (SAS) AF: 0.928 AC: 9407 AN: 10136

European-Finnish (FIN) AF: 0.877 AC: 3020 AN: 3442

Middle Eastern (MID) AF: 0.956 AC: 285 AN: 298

European-Non Finnish (NFE) AF: 0.917 AC: 46006 AN: 50166

Other (OTH) AF: 0.901 AC: 3924 AN: 4356

GnomAD4 genome AF: 0.892 AC: 135765 AN: 152250 Hom.: 60703 Cov.: 32 AF XY: 0.889 AC XY: 66173 AN XY: 74434

African (AFR) AF: 0.833 AC: 34606 AN: 41544

American (AMR) AF: 0.904 AC: 13835 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3182 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4139 AN: 5168

South Asian (SAS) AF: 0.927 AC: 4477 AN: 4828

European-Finnish (FIN) AF: 0.870 AC: 9225 AN: 10598

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63259 AN: 68026

Other (OTH) AF: 0.894 AC: 1882 AN: 2106

Alfa AF: 0.906 Hom.: 7756

Bravo AF: 0.893

Asia WGS AF: 0.845 AC: 2942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs4887075; hg19: chr15-78953131;