16-20046339-G-C

Position:

• chr16-20046339-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570682.2(GPR139):​c.128-13670C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,182 control chromosomes in the GnomAD database, including 3,346 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 (3346 hom., cov: 33)
• Consequence: GPR139 ENST00000570682.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR139	NM_001002911.4	c.128-13670C>G		intron_variant		ENST00000570682.2	NP_001002911.1
GPR139	NM_001318483.1	c.-152-13670C>G		intron_variant			NP_001305412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR139	ENST00000570682.2	c.128-13670C>G		intron_variant		1	NM_001002911.4	ENSP00000458791	P1
GPR139	ENST00000326571.7	c.*74-13670C>G		intron_variant, NMD_transcript_variant		1		ENSP00000370779

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28629 AN: 152064 Hom.: 3347 Cov.: 33

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.188 AC: 28632 AN: 152182 Hom.: 3346 Cov.: 33 AF XY: 0.193 AC XY: 14383 AN XY: 74380

Gnomad4 AFR AF: 0.0592

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.184

Alfa AF: 0.210 Hom.: 469

Bravo AF: 0.174

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1902813; hg19: chr16-20057661;