chr15-78727236-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000564933.6(GOLGA6GP):​n.60G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6GP ENST00000564933.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000564933.6. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6GP	ENST00000564933.6	TSL:6	n.60G>A		non_coding_transcript_exon	Exon 1 of 13
	CHRNB4	ENST00000558216.1	TSL:2	n.143+376C>T		intron	N/A
	ENSG00000290426	ENST00000565476.5	TSL:4	n.373-1716G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 381254 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 217074

African (AFR) AF: 0.00 AC: 0 AN: 10420

American (AMR) AF: 0.00 AC: 0 AN: 35846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11644

East Asian (EAS) AF: 0.00 AC: 0 AN: 13230

South Asian (SAS) AF: 0.00 AC: 0 AN: 67406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 191854

Other (OTH) AF: 0.00 AC: 0 AN: 16650

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.90
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;