10-123687995-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_153442.4(GPR26):c.849G>A(p.Ala283=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,613,968 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (168 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (151 hom.)
• Consequence: GPR26 NM_153442.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.812

Genes affected

GPR26 (HGNC:4481): (G protein-coupled receptor 26) This gene encodes a G protein-couple receptor protein. G-protein-coupled receptors are a large family of membrane proteins that are involved in cellular responses to environmental stimuli, neurotransmitters, and hormones. The encoded protein may play a role in neurodegenerative diseases. Epigenetic silencing of this gene has been observed in gliomas. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 10-123687995-G-A is Benign according to our data. Variant chr10-123687995-G-A is described in ClinVar as [Benign]. Clinvar id is 776548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.812 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR26	NM_153442.4	c.849G>A	p.Ala283=	synonymous_variant	3/3	ENST00000284674.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR26	ENST00000284674.2	c.849G>A	p.Ala283=	synonymous_variant	3/3	1	NM_153442.4	P1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3923 AN: 152140 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00690 AC: 1735 AN: 251360 Hom.: 69 AF XY: 0.00500 AC XY: 679 AN XY: 135864

Gnomad AFR exome AF: 0.0913

Gnomad AMR exome AF: 0.00555

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00257 AC: 3760 AN: 1461710 Hom.: 151 Cov.: 32 AF XY: 0.00216 AC XY: 1568 AN XY: 727158

Gnomad4 AFR exome AF: 0.0851

Gnomad4 AMR exome AF: 0.00639

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.00722

GnomAD4 genome AF: 0.0258 AC: 3921 AN: 152258 Hom.: 168 Cov.: 33 AF XY: 0.0247 AC XY: 1840 AN XY: 74452

Gnomad4 AFR AF: 0.0885

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0108 Hom.: 22

Bravo AF: 0.0294

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	15
Dann	Benign	0.87

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

Other links and lift over

dbSNP: rs62640899; hg19: chr10-125447511; COSMIC: COSV52937379;