NM_007223.3:c.173-12860C>T

Variant names:

• chr15-39820118-G-A
• rs275715
• NM_007223.3:c.173-12860C>T

Variant summary

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

The NM_007223.3(GPR176):​c.173-12860C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,196 control chromosomes in the GnomAD database, including 1,880 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 0.094 (1880 hom., cov: 32)
• Consequence: GPR176 NM_007223.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 2 publications found

Genes affected

GPR176 (HGNC:32370): (G protein-coupled receptor 176) Members of the G protein-coupled receptor family, such as GPR176, are cell surface receptors involved in responses to hormones, growth factors, and neurotransmitters (Hata et al., 1995 [PubMed 7893747]).[supplied by OMIM, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007223.3. 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
	GPR176	NM_007223.3	MANE Select	c.173-12860C>T		intron	N/A	NP_009154.1	Q14439-1
	GPR176	NM_001271854.2		c.173-12493C>T		intron	N/A	NP_001258783.1	Q14439-3
	GPR176	NM_001271855.2		c.37+8963C>T		intron	N/A	NP_001258784.1	Q14439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR176	ENST00000561100.2	TSL:1 MANE Select	c.173-12860C>T		intron	N/A	ENSP00000453076.1	Q14439-1
	GPR176	ENST00000299092.4	TSL:1	c.173-12493C>T		intron	N/A	ENSP00000299092.3	Q14439-3
	GPR176	ENST00000543580.7	TSL:2	c.37+8963C>T		intron	N/A	ENSP00000439361.1	Q14439-2

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14330 AN: 152078 Hom.: 1867 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0945 AC: 14378 AN: 152196 Hom.: 1880 Cov.: 32 AF XY: 0.0913 AC XY: 6798 AN XY: 74426

African (AFR) AF: 0.295 AC: 12213 AN: 41456

American (AMR) AF: 0.0388 AC: 593 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 88 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.0158 AC: 76 AN: 4824

European-Finnish (FIN) AF: 0.0284 AC: 302 AN: 10618

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 920 AN: 68028

Other (OTH) AF: 0.0725 AC: 153 AN: 2110

Alfa AF: 0.0347 Hom.: 336

Bravo AF: 0.106

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.6
DANN	Benign	0.78
PhyloP100		0.16
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: rs275715; hg19: chr15-40112319;