NM_001002911.4:c.128-16839G>A

Variant names:

• chr16-20049508-C-T
• rs12931939
• NM_001002911.4:c.128-16839G>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.128-16839G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,188 control chromosomes in the GnomAD database, including 2,994 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 0.18 (2994 hom., cov: 33)
• Consequence: GPR139 NM_001002911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR139	NM_001002911.4	c.128-16839G>A		intron_variant	Intron 1 of 1	ENST00000570682.2	NP_001002911.1
GPR139	NM_001318483.1	c.-152-16839G>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.128-16839G>A		intron_variant	Intron 1 of 1	1	NM_001002911.4	ENSP00000458791.2
GPR139	ENST00000326571.7	n.*74-16839G>A		intron_variant	Intron 2 of 2	1		ENSP00000370779.5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26888 AN: 152070 Hom.: 2996 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.177 AC: 26881 AN: 152188 Hom.: 2994 Cov.: 33 AF XY: 0.182 AC XY: 13538 AN XY: 74390

African (AFR) AF: 0.0539 AC: 2239 AN: 41522

American (AMR) AF: 0.187 AC: 2864 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.376 AC: 1943 AN: 5172

South Asian (SAS) AF: 0.170 AC: 819 AN: 4814

European-Finnish (FIN) AF: 0.308 AC: 3258 AN: 10570

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14494 AN: 68022

Other (OTH) AF: 0.172 AC: 363 AN: 2112

Alfa AF: 0.192 Hom.: 8912

Bravo AF: 0.165

Asia WGS AF: 0.213 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		0.28
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: rs12931939; hg19: chr16-20060830;