chr9-77794222-C-G

Variant names:

• chr9-77794222-C-G
• rs1328530
• NM_002072.5:c.735+241G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002072.5(GNAQ):​c.735+241G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,956 control chromosomes in the GnomAD database, including 25,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (25363 hom., cov: 32)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.539
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 9-77794222-C-G is Benign according to our data. Variant chr9-77794222-C-G is described in ClinVar as Benign. ClinVar VariationId is 1286804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 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+241G>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+241G>C		intron	N/A	ENSP00000286548.4	P50148
	GNAQ	ENST00000857199.1		c.810+241G>C		intron	N/A	ENSP00000527258.1
	GNAQ	ENST00000915940.1		c.735+241G>C		intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83281 AN: 151838 Hom.: 25361 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.579

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.548 AC: 83306 AN: 151956 Hom.: 25363 Cov.: 32 AF XY: 0.547 AC XY: 40647 AN XY: 74258

African (AFR) AF: 0.268 AC: 11085 AN: 41434

American (AMR) AF: 0.602 AC: 9181 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2263 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2464 AN: 5160

South Asian (SAS) AF: 0.598 AC: 2885 AN: 4822

European-Finnish (FIN) AF: 0.650 AC: 6870 AN: 10564

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46447 AN: 67936

Other (OTH) AF: 0.581 AC: 1228 AN: 2112

Alfa AF: 0.474 Hom.: 1552

Bravo AF: 0.531

Asia WGS AF: 0.566 AC: 1970 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1328530; hg19: chr9-80409138;