dbSNP rs35756741: GPR19:c.-261G>A (chr12-12715767-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 XM_011520623.4(GPR19):c.-261G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 152,260 control chromosomes in the GnomAD database, including 502 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 0.070 ( 502 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

GPR19
XM_011520623.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.305

Publications

8 publications found

Variant links:

Genes affected

GPR19 (HGNC:4473): (G protein-coupled receptor 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

GPR19 links:

CDKN1B (HGNC:1785): (cyclin dependent kinase inhibitor 1B) This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4). [provided by RefSeq, Apr 2014]

CDKN1B Gene-Disease associations (from GenCC):

multiple endocrine neoplasia type 4
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen
multiple endocrine neoplasia
Inheritance: AD Classification: STRONG Submitted by: G2P
hereditary nonpolyposis colon cancer
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

CDKN1B 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=-0.73).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR19	XM_011520623.4 link	c.-261G>A		5_prime_UTR_variant	Exon 1 of 4		XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN1B	ENST00000477087.1 link	n.48-10C>T	intron_variant	Intron 1 of 3	3
CDKN1B	ENST00000682620.1 link	n.1631-3058C>T	intron_variant	Intron 2 of 3
CDKN1B	ENST00000684771.1 link	n.585-3058C>T	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0703

AC:

10698

AN:

152118

Hom.:

498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0303

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0562

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0917

Gnomad OTH

AF:

0.0705

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.143

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0703

AC:

10709

AN:

152236

Hom.:

502

Cov.:

AF XY:

0.0711

AC XY:

5293

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0304

AC:

1265

AN:

41552

American (AMR)

AF:

0.0560

AC:

857

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3470

East Asian (EAS)

AF:

0.00327

AC:

AN:

5192

South Asian (SAS)

AF:

0.127

AC:

614

AN:

4816

European-Finnish (FIN)

AF:

0.105

AC:

1108

AN:

10592

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0917

AC:

6238

AN:

68010

Other (OTH)

AF:

0.0697

AC:

147

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

495

989

1484

1978

2473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0767

Hom.:

Bravo

AF:

0.0636

Asia WGS

AF:

0.0690

AC:

242

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.8

(source)

DANN

Benign

0.91

PhyloP100

-0.30

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

Computational scores

Splicing

Publications

Other links and lift over