9-77728671-G-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002072.5(GNAQ):c.736-5_736-4insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (28650 hom., cov: 0)
  • Exomes 𝑓: 0.46 (11433 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNAQ NM_002072.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.572

Genes affected

GNAQ (HGNC:4390): (G protein subunit alpha q) This locus encodes a guanine nucleotide-binding protein. The encoded protein, an alpha subunit in the Gq class, couples a seven-transmembrane domain receptor to activation of phospolipase C-beta. Mutations at this locus have been associated with problems in platelet activation and aggregation. A related pseudogene exists on chromosome 2.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-77728671-G-GA is Benign according to our data. Variant chr9-77728671-G-GA is described in ClinVar as [Benign]. Clinvar id is 768309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAQ	NM_002072.5	c.736-5_736-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286548.9
GNAQ	XM_047423239.1	c.562-5_562-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
GNAQ	XM_047423240.1	c.562-5_562-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAQ	ENST00000286548.9	c.736-5_736-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002072.5	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 90799 AN: 145520 Hom.: 28662 Cov.: 0

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.702

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.638

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.456 AC: 531446 AN: 1165842 Hom.: 11433 Cov.: 22 AF XY: 0.455 AC XY: 266289 AN XY: 584788

Gnomad4 AFR exome AF: 0.372

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.387

Gnomad4 SAS exome AF: 0.433

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.624 AC: 90796 AN: 145586 Hom.: 28650 Cov.: 0 AF XY: 0.619 AC XY: 43713 AN XY: 70562

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.637

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

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Computational scores

Source: dbNSFP v4.3

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: rs5898555; hg19: chr9-80343587;