16-20048355-C-T

Variant names:

• chr16-20048355-C-T
• rs12926725
• NM_001002911.4:c.128-15686G>A

Variant summary

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

The NM_001002911.4(GPR139):​c.128-15686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,038 control chromosomes in the GnomAD database, including 3,313 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 0.19 (3313 hom., cov: 32)
• Consequence: GPR139 NM_001002911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 5 publications found

Genes affected

GPR139 (HGNC:19995): (G protein-coupled receptor 139) This gene encodes a member of the rhodopsin family of G-protein-coupled receptors. The encoded protein is almost exclusively expressed in the central nervous system. L-tryptophan and L-phenylalanine may act as the physiologic ligands of the encoded protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR139	NM_001002911.4	c.128-15686G>A		intron_variant	Intron 1 of 1	ENST00000570682.2	NP_001002911.1
GPR139	NM_001318483.1	c.-152-15686G>A		intron_variant	Intron 2 of 2		NP_001305412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR139	ENST00000570682.2	c.128-15686G>A		intron_variant	Intron 1 of 1	1	NM_001002911.4	ENSP00000458791.2
GPR139	ENST00000326571.7	n.*74-15686G>A		intron_variant	Intron 2 of 2	1		ENSP00000370779.5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28415 AN: 151920 Hom.: 3314 Cov.: 32

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.187 AC: 28418 AN: 152038 Hom.: 3313 Cov.: 32 AF XY: 0.192 AC XY: 14279 AN XY: 74292

African (AFR) AF: 0.0585 AC: 2428 AN: 41486

American (AMR) AF: 0.191 AC: 2914 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1889 AN: 5162

South Asian (SAS) AF: 0.165 AC: 792 AN: 4810

European-Finnish (FIN) AF: 0.327 AC: 3452 AN: 10546

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15603 AN: 67972

Other (OTH) AF: 0.184 AC: 387 AN: 2108

Alfa AF: 0.176 Hom.: 1740

Bravo AF: 0.174

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.90
DANN	Benign	0.56
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12926725; hg19: chr16-20059677;