rs2127900

Variant names:

• chr15-78715219-G-A
• rs2127900
• ENST00000558216.1:n.144-7114C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78715219-G-A
• chr15-78715219-G-C

Variant summary

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

The ENST00000558216.1(CHRNB4):​n.144-7114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,258 control chromosomes in the GnomAD database, including 68,795 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 0.95 (68795 hom., cov: 32)
• Consequence: CHRNB4 ENST00000558216.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370913	XR_932508.2	n.1348-7114C>T		intron_variant	Intron 1 of 2
LOC105370913	XR_932509.2	n.1304-7114C>T		intron_variant	Intron 1 of 2
LOC105370913	XR_932510.3	n.449+393C>T		intron_variant	Intron 1 of 2
LOC105370913	XR_932511.3	n.257+3149C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000558216.1	n.144-7114C>T		intron_variant	Intron 1 of 2	2
CHRNB4	ENST00000560511.5	n.110+4958C>T		intron_variant	Intron 1 of 6	3
ENSG00000290426	ENST00000565476.5	n.317-4086G>A		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144617 AN: 152140 Hom.: 68752 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.946

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.950 AC: 144719 AN: 152258 Hom.: 68795 Cov.: 32 AF XY: 0.948 AC XY: 70580 AN XY: 74438

African (AFR) AF: 0.932 AC: 38724 AN: 41538

American (AMR) AF: 0.914 AC: 13978 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3330 AN: 3472

East Asian (EAS) AF: 0.975 AC: 5052 AN: 5180

South Asian (SAS) AF: 0.967 AC: 4661 AN: 4818

European-Finnish (FIN) AF: 0.920 AC: 9755 AN: 10606

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

European-Non Finnish (NFE) AF: 0.972 AC: 66140 AN: 68032

Other (OTH) AF: 0.946 AC: 2000 AN: 2114

Alfa AF: 0.994 Hom.: 60586

Bravo AF: 0.948

Asia WGS AF: 0.965 AC: 3358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.29
DANN	Benign	0.59
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs2127900; hg19: chr15-79007561;