9-77725471-C-T

Variant names:

• chr9-77725471-C-T
• rs6560613
• NM_002072.5:c.889+3043G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002072.5(GNAQ):​c.889+3043G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 151,998 control chromosomes in the GnomAD database, including 67,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (67775 hom., cov: 28)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.889+3043G>A		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.889+3043G>A		intron	N/A	ENSP00000286548.4	P50148
	GNAQ	ENST00000857199.1		c.964+3043G>A		intron	N/A	ENSP00000527258.1
	GNAQ	ENST00000915940.1		c.889+3043G>A		intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143344 AN: 151880 Hom.: 67716 Cov.: 28

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.945

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

GnomAD4 genome AF: 0.944 AC: 143462 AN: 151998 Hom.: 67775 Cov.: 28 AF XY: 0.943 AC XY: 70071 AN XY: 74270

African (AFR) AF: 0.985 AC: 40870 AN: 41496

American (AMR) AF: 0.959 AC: 14623 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3237 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5163 AN: 5166

South Asian (SAS) AF: 0.945 AC: 4542 AN: 4806

European-Finnish (FIN) AF: 0.910 AC: 9578 AN: 10526

Middle Eastern (MID) AF: 0.945 AC: 276 AN: 292

European-Non Finnish (NFE) AF: 0.917 AC: 62331 AN: 67970

Other (OTH) AF: 0.946 AC: 1997 AN: 2112

Alfa AF: 0.933 Hom.: 40934

Bravo AF: 0.950

Asia WGS AF: 0.979 AC: 3404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.027
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: rs6560613; hg19: chr9-80340387;