Genetic Variant GPR6:c.-18-9C>T (chr6-109979086-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005284.5(GPR6):c.-18-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,560,916 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 82 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 76 hom. )

Consequence

GPR6
NM_005284.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00800

Publications

0 publications found

Variant links:

Genes affected

GPR6 (HGNC:4515): (G protein-coupled receptor 6) Predicted to enable sphingosine-1-phosphate receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway and regulation of metabolic process. Predicted to act upstream of or within positive regulation of cytosolic calcium ion concentration. Predicted to be integral component of plasma membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-109979086-C-T is Benign according to our data. Variant chr6-109979086-C-T is described in ClinVar as Benign. ClinVar VariationId is 783756.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR6	NM_005284.5 link	c.-18-9C>T		intron_variant	Intron 1 of 1	ENST00000275169.5	NP_005275.1	P46095-1F1DAM6
GPR6	NM_001286099.2 link	c.28-9C>T		intron_variant	Intron 2 of 2		NP_001273028.1	P46095-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR6	ENST00000275169.5 link	c.-18-9C>T		intron_variant	Intron 1 of 1	6	NM_005284.5	ENSP00000275169.3		P46095-1
GPR6	ENST00000414000.3 link	c.28-9C>T		intron_variant	Intron 2 of 2	2		ENSP00000406986.2		P46095-2

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2779

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00546

AC:

1065

AN:

195150

AF XY:

0.00382

show subpopulations

Gnomad AFR exome

AF:

0.0643

Gnomad AMR exome

AF:

0.00542

Gnomad ASJ exome

AF:

0.000311

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000341

Gnomad OTH exome

AF:

0.00252

GnomAD4 exome

AF:

0.00192

AC:

2710

AN:

1408626

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1194

AN XY:

698976

show subpopulations

African (AFR)

AF:

0.0632

AC:

1986

AN:

31428

American (AMR)

AF:

0.00558

AC:

202

AN:

36196

Ashkenazi Jewish (ASJ)

AF:

0.000478

AC:

AN:

23004

East Asian (EAS)

AF:

0.00

AC:

AN:

39488

South Asian (SAS)

AF:

0.0000632

AC:

AN:

79076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39058

Middle Eastern (MID)

AF:

0.00271

AC:

AN:

5532

European-Non Finnish (NFE)

AF:

0.000213

AC:

234

AN:

1096446

Other (OTH)

AF:

0.00440

AC:

257

AN:

58398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

157

314

471

628

785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0183

AC:

2782

AN:

152290

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1278

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0629

AC:

2615

AN:

41554

American (AMR)

AF:

0.00784

AC:

120

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68034

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

128

257

385

514

642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00829

Hom.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.9

(source)

DANN

Benign

0.94

PhyloP100

0.0080

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over