15-78727236-G-T

Variant names:

• chr15-78727236-G-T
• rs899997
• ENST00000564933.6:n.60G>T

Variant summary

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

The ENST00000564933.6(GOLGA6GP):​n.60G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 532,820 control chromosomes in the GnomAD database, including 111,394 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 0.58 (28277 hom., cov: 32)
  • Exomes 𝑓: 0.65 (83117 hom.)
• Consequence: GOLGA6GP ENST00000564933.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 29 publications found

Genes affected

GOLGA6GP (HGNC:55709): (golgin A6 family member G%2C pseudogene [Source:HGNC Symbol%3BAcc:HGNC:55709])

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370913	XR_932508.2	n.1347+332C>A		intron_variant	Intron 1 of 2
LOC105370913	XR_932509.2	n.1303+376C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6GP	ENST00000564933.6	n.60G>T		non_coding_transcript_exon_variant	Exon 1 of 13	6
CHRNB4	ENST00000558216.1	n.143+376C>A		intron_variant	Intron 1 of 2	2
ENSG00000290426	ENST00000565476.5	n.373-1716G>T		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87697 AN: 151762 Hom.: 28277 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.650 AC: 247543 AN: 380942 Hom.: 83117 Cov.: 2 AF XY: 0.649 AC XY: 140695 AN XY: 216896

African (AFR) AF: 0.285 AC: 2963 AN: 10408

American (AMR) AF: 0.526 AC: 18823 AN: 35800

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 7766 AN: 11632

East Asian (EAS) AF: 0.504 AC: 6668 AN: 13218

South Asian (SAS) AF: 0.545 AC: 36734 AN: 67346

European-Finnish (FIN) AF: 0.612 AC: 19679 AN: 32156

Middle Eastern (MID) AF: 0.678 AC: 1369 AN: 2018

European-Non Finnish (NFE) AF: 0.744 AC: 142646 AN: 191718

Other (OTH) AF: 0.655 AC: 10895 AN: 16646

GnomAD4 genome AF: 0.578 AC: 87711 AN: 151878 Hom.: 28277 Cov.: 32 AF XY: 0.572 AC XY: 42429 AN XY: 74206

African (AFR) AF: 0.281 AC: 11619 AN: 41400

American (AMR) AF: 0.600 AC: 9172 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2325 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2499 AN: 5150

South Asian (SAS) AF: 0.539 AC: 2592 AN: 4812

European-Finnish (FIN) AF: 0.599 AC: 6319 AN: 10542

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51031 AN: 67916

Other (OTH) AF: 0.593 AC: 1252 AN: 2110

Alfa AF: 0.680 Hom.: 92947

Bravo AF: 0.566

Asia WGS AF: 0.457 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.61
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs899997; hg19: chr15-79019578; COSMIC: COSV73739319;