9-77969093-G-T

Variant names:

• chr9-77969093-G-T
• rs4745679
• NM_002072.5:c.137-46748C>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.137-46748C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,070 control chromosomes in the GnomAD database, including 13,122 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 0.40 (13122 hom., cov: 33)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953
• Publications: 3 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000307361 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.474 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	NM_002072.5	MANE Select	c.137-46748C>A		intron	N/A	NP_002063.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAQ	ENST00000286548.9	TSL:1 MANE Select	c.137-46748C>A		intron	N/A	ENSP00000286548.4
	GNAQ	ENST00000411677.1	TSL:3	c.50-46748C>A		intron	N/A	ENSP00000391501.1
	ENSG00000307361	ENST00000825387.1		n.162-1116C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61344 AN: 151952 Hom.: 13121 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.403 AC: 61355 AN: 152070 Hom.: 13122 Cov.: 33 AF XY: 0.402 AC XY: 29857 AN XY: 74324

African (AFR) AF: 0.292 AC: 12100 AN: 41480

American (AMR) AF: 0.483 AC: 7378 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1320 AN: 3470

East Asian (EAS) AF: 0.168 AC: 872 AN: 5176

South Asian (SAS) AF: 0.323 AC: 1560 AN: 4824

European-Finnish (FIN) AF: 0.473 AC: 4994 AN: 10558

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.466 AC: 31679 AN: 67980

Other (OTH) AF: 0.388 AC: 818 AN: 2108

Alfa AF: 0.332 Hom.: 1189

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.67
PhyloP100		-0.95
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: rs4745679; hg19: chr9-80584009;