Genetic Variant NM_016235.3:c.-1-117G>A (chr16-19872963-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016235.3(GPRC5B):c.-1-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 708,102 control chromosomes in the GnomAD database, including 163,599 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 0.69 ( 36945 hom., cov: 32)

Exomes 𝑓: 0.67 ( 126654 hom. )

Consequence

GPRC5B
NM_016235.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

megalencephalic leukoencephalopathy with subcortical cysts 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
megalencephalic leukoencephalopathy with subcortical cysts 3
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

GPRC5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5B	NM_016235.3 link	c.-1-117G>A		intron_variant	Intron 1 of 3	ENST00000300571.7	NP_057319.1	Q9NZH0-1A0A024QYX2
GPRC5B	NM_001304771.1 link	c.393-117G>A		intron_variant	Intron 1 of 3		NP_001291700.1	B7Z831

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5B	ENST00000300571.7 link	c.-1-117G>A		intron_variant	Intron 1 of 3	1	NM_016235.3	ENSP00000300571.2		Q9NZH0-1

Frequencies

GnomAD3 genomes

AF:

0.693

AC:

105256

AN:

151944

Hom.:

36912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.798

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.706

GnomAD4 exome

AF:

0.670

AC:

372449

AN:

556040

Hom.:

126654

AF XY:

0.672

AC XY:

197564

AN XY:

294084

show subpopulations

African (AFR)

AF:

0.776

AC:

11614

AN:

14968

American (AMR)

AF:

0.504

AC:

12703

AN:

25192

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

11864

AN:

15092

East Asian (EAS)

AF:

0.868

AC:

28905

AN:

33300

South Asian (SAS)

AF:

0.687

AC:

36260

AN:

52768

European-Finnish (FIN)

AF:

0.608

AC:

19793

AN:

32552

Middle Eastern (MID)

AF:

0.753

AC:

2092

AN:

2778

European-Non Finnish (NFE)

AF:

0.655

AC:

228781

AN:

349402

Other (OTH)

AF:

0.682

AC:

20437

AN:

29988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6783

13567

20350

27134

33917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2226

4452

6678

8904

11130

<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:

0.693

AC:

105333

AN:

152062

Hom.:

36945

Cov.:

AF XY:

0.692

AC XY:

51427

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.778

AC:

32276

AN:

41506

American (AMR)

AF:

0.596

AC:

9096

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.798

AC:

2768

AN:

3470

East Asian (EAS)

AF:

0.851

AC:

4390

AN:

5158

South Asian (SAS)

AF:

0.704

AC:

3390

AN:

4816

European-Finnish (FIN)

AF:

0.614

AC:

6485

AN:

10564

Middle Eastern (MID)

AF:

0.731

AC:

215

AN:

294

European-Non Finnish (NFE)

AF:

0.655

AC:

44545

AN:

67974

Other (OTH)

AF:

0.709

AC:

1495

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1623

3245

4868

6490

8113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.668

Hom.:

11665

Bravo

AF:

0.697

Asia WGS

AF:

0.780

AC:

2711

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0050

(source)

DANN

Benign

0.64

PhyloP100

-2.0

PromoterAI

-0.0026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over