9-77728671-G-GAA

Position:

• chr9-77728671-G-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002072.5(GNAQ):​c.736-5_736-4insTT 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 0.0439 in 1,298,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.049 (0 hom.)
• Consequence: GNAQ NM_002072.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter 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 -10 ACMG points.

• BP6: Variant 9-77728671-G-GAA is Benign according to our data. Variant chr9-77728671-G-GAA is described in ClinVar as [Benign]. Clinvar id is 770953.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAQ	NM_002072.5	c.736-5_736-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286548.9
GNAQ	XM_047423239.1	c.562-5_562-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
GNAQ	XM_047423240.1	c.562-5_562-4insTT		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_736-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002072.5	P1

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 207 AN: 145514 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00143

Gnomad ASJ AF: 0.000585

Gnomad EAS AF: 0.00303

Gnomad SAS AF: 0.000647

Gnomad FIN AF: 0.00391

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.00151

GnomAD4 exome AF: 0.0493 AC: 56832 AN: 1153140 Hom.: 0 Cov.: 22 AF XY: 0.0482 AC XY: 27878 AN XY: 578696

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.0331

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.0243

Gnomad4 SAS exome AF: 0.0406

Gnomad4 FIN exome AF: 0.0344

Gnomad4 NFE exome AF: 0.0535

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.00143 AC: 208 AN: 145580 Hom.: 0 Cov.: 0 AF XY: 0.00154 AC XY: 109 AN XY: 70566

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00143

Gnomad4 ASJ AF: 0.000585

Gnomad4 EAS AF: 0.00304

Gnomad4 SAS AF: 0.000650

Gnomad4 FIN AF: 0.00391

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.00150

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

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	Jul 24, 2017	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;