chr12-12661285-C-T

Variant names:

• chr12-12661285-C-T
• rs73279483
• NM_006143.3:c.1164G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_006143.3(GPR19):​c.1164G>A​(p.Ser388Ser) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.04
• Publications: 0 publications found

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]

ENSG00000257004 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: 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: Synonymous conserved (PhyloP=-2.04 with no splicing effect.
• BS1: 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR19	NM_006143.3	c.1164G>A	p.Ser388Ser	synonymous_variant	Exon 4 of 4	ENST00000651487.1	NP_006134.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR19	ENST00000651487.1	c.1164G>A	p.Ser388Ser	synonymous_variant	Exon 4 of 4		NM_006143.3	ENSP00000498976.1
GPR19	ENST00000332427.6	c.1164G>A	p.Ser388Ser	synonymous_variant	Exon 4 of 4	4		ENSP00000333744.2
GPR19	ENST00000540510.1	c.1164G>A	p.Ser388Ser	synonymous_variant	Exon 2 of 2	2		ENSP00000441832.1
ENSG00000257004	ENST00000817557.1	n.465+3321C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 785 AN: 152058 Hom.: 8 Cov.: 33

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

GnomAD2 exomes AF: 0.00149 AC: 374 AN: 251446 AF XY: 0.00107

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 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

African (AFR) AF: 0.0189 AC: 633 AN: 33468

American (AMR) AF: 0.000738 AC: 33 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111522

Other (OTH) AF: 0.000977 AC: 59 AN: 60378

GnomAD4 genome AF: 0.00517 AC: 786 AN: 152176 Hom.: 8 Cov.: 33 AF XY: 0.00505 AC XY: 376 AN XY: 74384

African (AFR) AF: 0.0180 AC: 746 AN: 41524

American (AMR) AF: 0.00183 AC: 28 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00204 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

Submissions by phenotype

not provided Benign:1

Mar 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.9
DANN	Benign	0.73
PhyloP100		-2.0
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs73279483; hg19: chr12-12814219;