16-20039144-C-G

Variant names:

• chr16-20039144-C-G
• rs868554
• NM_001002911.4:c.128-6475G>C

Variant summary

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

The NM_001002911.4(GPR139):​c.128-6475G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,174 control chromosomes in the GnomAD database, including 3,523 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 (3523 hom., cov: 32)
• Consequence: GPR139 NM_001002911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649
• Publications: 6 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR139	NM_001002911.4	c.128-6475G>C		intron_variant	Intron 1 of 1	ENST00000570682.2	NP_001002911.1
GPR139	NM_001318483.1	c.-152-6475G>C		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.128-6475G>C		intron_variant	Intron 1 of 1	1	NM_001002911.4	ENSP00000458791.2
GPR139	ENST00000326571.7	n.*74-6475G>C		intron_variant	Intron 2 of 2	1		ENSP00000370779.5

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29100 AN: 152056 Hom.: 3518 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.191 AC: 29115 AN: 152174 Hom.: 3523 Cov.: 32 AF XY: 0.195 AC XY: 14471 AN XY: 74384

African (AFR) AF: 0.0526 AC: 2185 AN: 41538

American (AMR) AF: 0.176 AC: 2701 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1810 AN: 5156

South Asian (SAS) AF: 0.186 AC: 896 AN: 4828

European-Finnish (FIN) AF: 0.323 AC: 3404 AN: 10554

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16808 AN: 68002

Other (OTH) AF: 0.199 AC: 422 AN: 2116

Alfa AF: 0.118 Hom.: 215

Bravo AF: 0.173

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.8
DANN	Benign	0.59
PhyloP100		0.65
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: rs868554; hg19: chr16-20050466;