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GeneBe

12-12661285-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006143.3(GPR19):c.1164G>A(p.Ser388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,613,500 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00051 ( 2 hom. )

Consequence

GPR19
NM_006143.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-12661285-C-T is Benign according to our data. Variant chr12-12661285-C-T is described in ClinVar as [Benign]. Clinvar id is 723538.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.04 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00517 (786/152176) while in subpopulation AFR AF= 0.018 (746/41524). AF 95% confidence interval is 0.0169. There are 8 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR19NM_006143.3 linkuse as main transcriptc.1164G>A p.Ser388= synonymous_variant 4/4 ENST00000651487.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR19ENST00000651487.1 linkuse as main transcriptc.1164G>A p.Ser388= synonymous_variant 4/4 NM_006143.3 P1
GPR19ENST00000332427.6 linkuse as main transcriptc.1164G>A p.Ser388= synonymous_variant 4/44 P1
GPR19ENST00000540510.1 linkuse as main transcriptc.1164G>A p.Ser388= synonymous_variant 2/22 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00516
AC:
785
AN:
152058
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
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:
0.00383
GnomAD3 exomes
AF:
0.00149
AC:
374
AN:
251446
Hom.:
2
AF XY:
0.00107
AC XY:
146
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.0209
Gnomad AMR exome
AF:
0.000636
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000514
AC:
751
AN:
1461324
Hom.:
2
Cov.:
30
AF XY:
0.000448
AC XY:
326
AN XY:
727022
show subpopulations
Gnomad4 AFR exome
AF:
0.0189
Gnomad4 AMR exome
AF:
0.000738
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.000977
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00517
AC:
786
AN:
152176
Hom.:
8
Cov.:
33
AF XY:
0.00505
AC XY:
376
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0180
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00218
Hom.:
0
Bravo
AF:
0.00569
Asia WGS
AF:
0.000577
AC:
3
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 02, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
1.9
Dann
Benign
0.73

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.

Other links and lift over

dbSNP: rs73279483; hg19: chr12-12814219; API