chr1-168121793-C-A

Variant names:

• chr1-168121793-C-A
• rs11586522
• NM_001375883.1:c.-45+14946G>T

Variant summary

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

The NM_001375883.1(GPR161):​c.-45+14946G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,154 control chromosomes in the GnomAD database, including 4,073 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 0.22 (4073 hom., cov: 32)
• Consequence: GPR161 NM_001375883.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

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.-45+14946G>T		intron	N/A	NP_001362812.1	Q8N6U8-1
	GPR161	NM_001267609.1		c.16+13113G>T		intron	N/A	NP_001254538.1	Q8N6U8-6
	GPR161	NM_001267611.1		c.7+15597G>T		intron	N/A	NP_001254540.1	A0A0A0MQW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR161	ENST00000682931.1	MANE Select	c.-45+14946G>T		intron	N/A	ENSP00000506967.1	Q8N6U8-1
	GPR161	ENST00000271357.9	TSL:1	c.7+15597G>T		intron	N/A	ENSP00000271357.6	A0A0A0MQW8
	GPR161	ENST00000367838.5	TSL:1	c.-138-7244G>T		intron	N/A	ENSP00000356812.1	Q8N6U8-1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33028 AN: 152036 Hom.: 4069 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.217 AC: 33043 AN: 152154 Hom.: 4073 Cov.: 32 AF XY: 0.218 AC XY: 16229 AN XY: 74394

African (AFR) AF: 0.126 AC: 5227 AN: 41536

American (AMR) AF: 0.371 AC: 5681 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3472

East Asian (EAS) AF: 0.157 AC: 808 AN: 5160

South Asian (SAS) AF: 0.192 AC: 926 AN: 4816

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10592

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16464 AN: 67966

Other (OTH) AF: 0.231 AC: 489 AN: 2116

Alfa AF: 0.144 Hom.: 387

Bravo AF: 0.230

Asia WGS AF: 0.170 AC: 591 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.60
DANN	Benign	0.79
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11586522; hg19: chr1-168091031;