NM_001375883.1:c.1396T>C

Variant names:

• chr1-168085725-A-G
• rs367790399
• NM_001375883.1:c.1396T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001375883.1(GPR161):​c.1396T>C​(p.Leu466Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,254 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (47 hom.)
• Consequence: GPR161 NM_001375883.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.516
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-168085725-A-G is Benign according to our data. Variant chr1-168085725-A-G is described in ClinVar as Benign. ClinVar VariationId is 788083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.516 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000787 (120/152382) while in subpopulation SAS AF = 0.023 (111/4828). AF 95% confidence interval is 0.0195. There are 1 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 120 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.1396T>C	p.Leu466Leu	synonymous	Exon 6 of 6	NP_001362812.1	Q8N6U8-1
	GPR161	NM_001267609.1		c.1456T>C	p.Leu486Leu	synonymous	Exon 7 of 7	NP_001254538.1	Q8N6U8-6
	GPR161	NM_001267611.1		c.1447T>C	p.Leu483Leu	synonymous	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.1396T>C	p.Leu466Leu	synonymous	Exon 6 of 6	ENSP00000506967.1	Q8N6U8-1
	GPR161	ENST00000271357.9	TSL:1	c.1447T>C	p.Leu483Leu	synonymous	Exon 6 of 6	ENSP00000271357.6	A0A0A0MQW8
	GPR161	ENST00000367838.5	TSL:1	c.1396T>C	p.Leu466Leu	synonymous	Exon 8 of 8	ENSP00000356812.1	Q8N6U8-1

Frequencies

GnomAD3 genomes AF: 0.000788 AC: 120 AN: 152264 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000964

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00285 AC: 717 AN: 251412 AF XY: 0.00369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00145 AC: 2114 AN: 1461872 Hom.: 47 Cov.: 32 AF XY: 0.00200 AC XY: 1455 AN XY: 727240

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0223 AC: 1927 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000800 AC: 89 AN: 1111996

Other (OTH) AF: 0.00154 AC: 93 AN: 60396

GnomAD4 genome AF: 0.000787 AC: 120 AN: 152382 Hom.: 1 Cov.: 32 AF XY: 0.00110 AC XY: 82 AN XY: 74512

African (AFR) AF: 0.0000962 AC: 4 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15312

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000327 Hom.: 1

Bravo AF: 0.000208

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		0.52
Mutation Taster		=100/0	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: rs367790399; hg19: chr1-168054963;