Variant 16-19861855-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_016235.3(GPRC5B):c.1149C>T(p.Val383Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,613,292 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 56 hom. )

Consequence

GPRC5B
NM_016235.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.339

Variant links:

Genes affected

GPRC5B (HGNC:13308): (G protein-coupled receptor class C group 5 member B) This gene encodes a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The encoded protein may modulate insulin secretion and increased protein expression is associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

GPRC5B links:

GPRC5B (HGNC:):

GPRC5B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 16-19861855-G-A is Benign according to our data. Variant chr16-19861855-G-A is described in ClinVar as [Benign]. Clinvar id is 769895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.339 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2205/152068) while in subpopulation AFR AF= 0.0397 (1646/41460). AF 95% confidence interval is 0.0381. There are 35 homozygotes in gnomad4. There are 1172 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2205 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5B	NM_016235.3 linkuse as main transcript	c.1149C>T	p.Val383Val	synonymous_variant	3/4	ENST00000300571.7	NP_057319.1	Q9NZH0-1A0A024QYX2
GPRC5B	NM_001304771.1 linkuse as main transcript	c.1542C>T	p.Val514Val	synonymous_variant	3/4		NP_001291700.1	B7Z831

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5B	ENST00000300571.7 linkuse as main transcript	c.1149C>T	p.Val383Val	synonymous_variant	3/4	1	NM_016235.3	ENSP00000300571.2		Q9NZH0-1

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2204

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0380

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00675

AC:

1696

AN:

251438

Hom.:

AF XY:

0.00587

AC XY:

798

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0435

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00273

AC:

3992

AN:

1461224

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

1792

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.0411

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0311

Gnomad4 NFE exome

AF:

0.000558

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.0145

AC:

2205

AN:

152068

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1172

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0397

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0380

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00656

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

4.7

DANN

Benign

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over