Genetic Variant GPR146:p.Ala187Ala (chr7-1058076-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001303473.2(GPR146):c.561C>T(p.Ala187Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000873 in 767,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

GPR146
NM_001303473.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.32

Variant links:

Genes affected

GPR146 (HGNC:21718): (G protein-coupled receptor 146) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR146 links:

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

C7orf50 links:

ENSG00000257607 (HGNC:):

ENSG00000257607 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=-5.32 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR146	NM_001303473.2 link	c.561C>T	p.Ala187Ala	synonymous_variant	Exon 2 of 2	ENST00000444847.2	NP_001290402.1	Q96CH1A4D2Q3B4DTD6
C7orf50	NM_001318252.2 link	c.130-47933G>A		intron_variant	Intron 2 of 4	ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR146	ENST00000444847.2 link	c.561C>T	p.Ala187Ala	synonymous_variant	Exon 2 of 2	2	NM_001303473.2	ENSP00000410743.2		Q96CH1
C7orf50	ENST00000397098.8 link	c.130-47933G>A		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3		Q9BRJ6

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

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:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000873

AC:

AN:

240620

AF XY:

0.0000533

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000764

AC:

AN:

614846

Hom.:

Cov.:

AF XY:

0.0000655

AC XY:

AN XY:

336052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17680

American (AMR)

AF:

0.000480

AC:

AN:

43712

Ashkenazi Jewish (ASJ)

AF:

0.0000477

AC:

AN:

20964

East Asian (EAS)

AF:

0.0000277

AC:

AN:

36048

South Asian (SAS)

AF:

0.0000143

AC:

AN:

69756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4020

European-Non Finnish (NFE)

AF:

0.0000515

AC:

AN:

349790

Other (OTH)

AF:

0.000152

AC:

AN:

32976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000131

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41470

American (AMR)

AF:

0.000850

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000314

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.36

(source)

DANN

Benign

0.86

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

chr7-1058076-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over