10-123666737-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_153442.4(GPR26):c.330C>T(p.Phe110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00608 in 1,598,366 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (6 hom., cov: 34)
  • Exomes 𝑓: 0.0062 (39 hom.)
• Consequence: GPR26 NM_153442.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0180

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-123666737-C-T is Benign according to our data. Variant chr10-123666737-C-T is described in ClinVar as [Benign]. Clinvar id is 788827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.018 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR26	NM_153442.4	c.330C>T	p.Phe110=	synonymous_variant	1/3	ENST00000284674.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR26	ENST00000284674.2	c.330C>T	p.Phe110=	synonymous_variant	1/3	1	NM_153442.4	P1

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 698 AN: 152184 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00889

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00453 AC: 988 AN: 218282 Hom.: 4 AF XY: 0.00478 AC XY: 577 AN XY: 120692

Gnomad AFR exome AF: 0.000690

Gnomad AMR exome AF: 0.00262

Gnomad ASJ exome AF: 0.00305

Gnomad EAS exome AF: 0.000656

Gnomad SAS exome AF: 0.00685

Gnomad FIN exome AF: 0.00113

Gnomad NFE exome AF: 0.00626

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00623 AC: 9015 AN: 1446064 Hom.: 39 Cov.: 30 AF XY: 0.00619 AC XY: 4449 AN XY: 719320

Gnomad4 AFR exome AF: 0.000601

Gnomad4 AMR exome AF: 0.00285

Gnomad4 ASJ exome AF: 0.00316

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.00725

Gnomad4 FIN exome AF: 0.00154

Gnomad4 NFE exome AF: 0.00695

Gnomad4 OTH exome AF: 0.00557

GnomAD4 genome AF: 0.00458 AC: 698 AN: 152302 Hom.: 6 Cov.: 34 AF XY: 0.00399 AC XY: 297 AN XY: 74472

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00681

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00573 Hom.: 1

Bravo AF: 0.00433

Asia WGS AF: 0.000867 AC: 3 AN: 3476

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.0
Dann	Benign	0.94

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: rs62640898; hg19: chr10-125426253;