rs2127900

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_932509.2(LOC105370913):​n.1304-7114C>T variant causes a intron, non coding transcript 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: LOC105370913 XR_932509.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512

Genes affected

LOC105370913 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LOC105370913	XR_932509.2	n.1304-7114C>T		intron_variant, non_coding_transcript_variant
LOC105370913	XR_932508.2	n.1348-7114C>T		intron_variant, non_coding_transcript_variant
LOC105370913	XR_932510.3	n.449+393C>T		intron_variant, non_coding_transcript_variant
LOC105370913	XR_932511.3	n.257+3149C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000558216.1	n.144-7114C>T		intron_variant, non_coding_transcript_variant		2
CHRNB4	ENST00000560511.5	n.110+4958C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000565476.5	n.317-4086G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.967

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.946

Alfa AF: 0.979 Hom.: 16894

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2127900; hg19: chr15-79007561;