9-77728671-GA-G

Variant summary

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

The NM_002072.5(GNAQ):c.736-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,295,286 control chromosomes in the GnomAD database, including 110 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (102 hom., cov: 0)
  • Exomes 𝑓: 0.031 (8 hom.)
• 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-GA-G is Benign according to our data. Variant chr9-77728671-GA-G is described in ClinVar as [Benign]. Clinvar id is 776427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-77728671-GA-G is described in Lovd as [Benign]. Variant chr9-77728671-GA-G is described in Lovd as [Benign]. Variant chr9-77728671-GA-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAQ	NM_002072.5	c.736-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286548.9
GNAQ	XM_047423239.1	c.562-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
GNAQ	XM_047423240.1	c.562-5del		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.736-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002072.5	P1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2659 AN: 145548 Hom.: 102 Cov.: 0

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00770

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00304

Gnomad SAS AF: 0.000647

Gnomad FIN AF: 0.00138

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.000511

Gnomad OTH AF: 0.0131

GnomAD4 exome AF: 0.0307 AC: 35312 AN: 1149670 Hom.: 8 Cov.: 22 AF XY: 0.0311 AC XY: 17934 AN XY: 576428

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0346

Gnomad4 EAS exome AF: 0.0668

Gnomad4 SAS exome AF: 0.0436

Gnomad4 FIN exome AF: 0.0354

Gnomad4 NFE exome AF: 0.0251

Gnomad4 OTH exome AF: 0.0360

GnomAD4 genome AF: 0.0184 AC: 2673 AN: 145616 Hom.: 102 Cov.: 0 AF XY: 0.0176 AC XY: 1240 AN XY: 70570

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.00769

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.00304

Gnomad4 SAS AF: 0.000650

Gnomad4 FIN AF: 0.00138

Gnomad4 NFE AF: 0.000512

Gnomad4 OTH AF: 0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 30, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

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;