rs899997

Positions:

• chr15-78727236-G-T

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

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

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=-0.91).
• 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/exons	MANE	UniProt
LOC105370913	XR_932509.2	n.1303+376C>A		intron_variant, non_coding_transcript_variant
LOC105370913	XR_932508.2	n.1347+332C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA6GP	ENST00000564933.6	n.60G>T		non_coding_transcript_exon_variant	1/13
CHRNB4	ENST00000558216.1	n.143+376C>A		intron_variant, non_coding_transcript_variant		2
	ENST00000565476.5	n.373-1716G>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.526

Gnomad4 ASJ exome AF: 0.668

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.545

Gnomad4 FIN exome AF: 0.612

Gnomad4 NFE exome AF: 0.744

Gnomad4 OTH exome AF: 0.655

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

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.593

Alfa AF: 0.712 Hom.: 36651

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

Splicing

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

Publications

LitVar

Other links and lift over

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