rs1328529

Variant names:

• chr9-77794429-A-G
• rs1328529
• NM_002072.5:c.735+34T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002072.5(GNAQ):​c.735+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,438,706 control chromosomes in the GnomAD database, including 207,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (16258 hom., cov: 31)
  • Exomes 𝑓: 0.53 (190778 hom.)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.605
• Publications: 8 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-77794429-A-G is Benign according to our data. Variant chr9-77794429-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 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.735+34T>C		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.735+34T>C		intron	N/A	ENSP00000286548.4	P50148
	GNAQ	ENST00000857199.1		c.810+34T>C		intron	N/A	ENSP00000527258.1
	GNAQ	ENST00000915940.1		c.735+34T>C		intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64389 AN: 151826 Hom.: 16260 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.451

GnomAD2 exomes AF: 0.481 AC: 105929 AN: 220078 AF XY: 0.492

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.454

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.534 AC: 686926 AN: 1286762 Hom.: 190778 Cov.: 16 AF XY: 0.533 AC XY: 343038 AN XY: 643084

African (AFR) AF: 0.131 AC: 3893 AN: 29628

American (AMR) AF: 0.456 AC: 17369 AN: 38102

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 12336 AN: 23448

East Asian (EAS) AF: 0.221 AC: 8207 AN: 37096

South Asian (SAS) AF: 0.438 AC: 31794 AN: 72648

European-Finnish (FIN) AF: 0.503 AC: 25229 AN: 50108

Middle Eastern (MID) AF: 0.478 AC: 1787 AN: 3742

European-Non Finnish (NFE) AF: 0.572 AC: 559095 AN: 977958

Other (OTH) AF: 0.504 AC: 27216 AN: 54032

GnomAD4 genome AF: 0.424 AC: 64381 AN: 151944 Hom.: 16258 Cov.: 31 AF XY: 0.419 AC XY: 31122 AN XY: 74258

African (AFR) AF: 0.152 AC: 6316 AN: 41486

American (AMR) AF: 0.474 AC: 7239 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1143 AN: 5158

South Asian (SAS) AF: 0.420 AC: 2021 AN: 4812

European-Finnish (FIN) AF: 0.490 AC: 5171 AN: 10554

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38925 AN: 67892

Other (OTH) AF: 0.448 AC: 946 AN: 2112

Alfa AF: 0.524 Hom.: 20319

Bravo AF: 0.409

Asia WGS AF: 0.307 AC: 1072 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.60
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: rs1328529; hg19: chr9-80409345; COSMIC: COSV54105959; COSMIC: COSV54105959;