1-168085622-C-G

Variant names:

• chr1-168085622-C-G
• rs1476203699
• NM_001375883.1:c.1499G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001375883.1(GPR161):​c.1499G>C​(p.Gly500Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: GPR161 NM_001375883.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

GPR161 (HGNC:23694): (G protein-coupled receptor 161) The protein encoded by this gene is an orphan G protein-coupled receptor whose ligand is unknown. This gene is overexpressed in triple-negative breast cancer, and disruption of this gene slows the proliferation of basal breast cancer cells. Therefore, this gene is a potential drug target for triple-negative breast cancer. [provided by RefSeq, Mar 2017]

GPR161 Gene-Disease associations (from GenCC):

• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08241597).
• BS2: High AC in GnomAdExome4 at 28 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375883.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR161	NM_001375883.1	MANE Select	c.1499G>C	p.Gly500Ala	missense	Exon 6 of 6	NP_001362812.1	Q8N6U8-1
	GPR161	NM_001267609.1		c.1559G>C	p.Gly520Ala	missense	Exon 7 of 7	NP_001254538.1	Q8N6U8-6
	GPR161	NM_001267611.1		c.1550G>C	p.Gly517Ala	missense	Exon 6 of 6	NP_001254540.1	A0A0A0MQW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR161	ENST00000682931.1	MANE Select	c.1499G>C	p.Gly500Ala	missense	Exon 6 of 6	ENSP00000506967.1	Q8N6U8-1
	GPR161	ENST00000271357.9	TSL:1	c.1550G>C	p.Gly517Ala	missense	Exon 6 of 6	ENSP00000271357.6	A0A0A0MQW8
	GPR161	ENST00000367838.5	TSL:1	c.1499G>C	p.Gly500Ala	missense	Exon 8 of 8	ENSP00000356812.1	Q8N6U8-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1461720 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727146

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.030
Sift	Benign	0.35	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.095
MutPred		0.31		Gain of catalytic residue at G500 (P = 0.0266)
MVP		0.66
MPC		0.34
ClinPred		0.10	T
GERP RS		3.8
Varity_R		0.038
gMVP		0.30
Mutation Taster		=79/21	polymorphism

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: rs1476203699; hg19: chr1-168054860;