9-77728671-GAAAAA-GAAAAAA

Variant names:

• chr9-77728671-G-GA
• rs5898555
• NM_002072.5:c.736-5dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002072.5(GNAQ):​c.736-5dupT variant causes a splice region, 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, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.572
• Publications: 5 publications found

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]

GNAQ Gene-Disease associations (from GenCC):

• congenital hemangioma

  Inheritance: AD Classification: STRONG Submitted by: G2P
• Sturge-Weber syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002072.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	NM_002072.5	MANE Select	c.736-5dupT		splice_region intron	N/A	NP_002063.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	ENST00000286548.9	TSL:1 MANE Select	c.736-5_736-4insT		splice_region intron	N/A	ENSP00000286548.4	P50148
	GNAQ	ENST00000857199.1		c.811-5_811-4insT		splice_region intron	N/A	ENSP00000527258.1
	GNAQ	ENST00000915940.1		c.736-5_736-4insT		splice_region intron	N/A	ENSP00000585999.1

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

GnomAD2 exomes AF: 0.461 AC: 78870 AN: 170990 AF XY: 0.464

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.405

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.466

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

African (AFR) AF: 0.372 AC: 9789 AN: 26302

American (AMR) AF: 0.445 AC: 12853 AN: 28900

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 9390 AN: 20942

East Asian (EAS) AF: 0.387 AC: 13720 AN: 35438

South Asian (SAS) AF: 0.433 AC: 29880 AN: 69022

European-Finnish (FIN) AF: 0.445 AC: 18805 AN: 42228

Middle Eastern (MID) AF: 0.463 AC: 2095 AN: 4522

European-Non Finnish (NFE) AF: 0.464 AC: 412844 AN: 889340

Other (OTH) AF: 0.449 AC: 22070 AN: 49148

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

African (AFR) AF: 0.483 AC: 19107 AN: 39580

American (AMR) AF: 0.679 AC: 9960 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2280 AN: 3422

East Asian (EAS) AF: 0.439 AC: 2163 AN: 4922

South Asian (SAS) AF: 0.604 AC: 2781 AN: 4602

European-Finnish (FIN) AF: 0.642 AC: 5599 AN: 8722

Middle Eastern (MID) AF: 0.688 AC: 190 AN: 276

European-Non Finnish (NFE) AF: 0.703 AC: 46760 AN: 66468

Other (OTH) AF: 0.637 AC: 1281 AN: 2010

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5898555; hg19: chr9-80343587;