rs4745672

Variant names:

• chr9-77883312-C-T
• rs4745672
• NM_002072.5:c.321+38849G>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.321+38849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,968 control chromosomes in the GnomAD database, including 10,525 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 0.34 (10525 hom., cov: 31)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAQ	NM_002072.5	c.321+38849G>A		intron_variant	Intron 2 of 6	ENST00000286548.9	NP_002063.2
GNAQ	XM_047423239.1	c.147+38849G>A		intron_variant	Intron 2 of 6		XP_047279195.1
GNAQ	XM_047423240.1	c.147+38849G>A		intron_variant	Intron 2 of 6		XP_047279196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAQ	ENST00000286548.9	c.321+38849G>A		intron_variant	Intron 2 of 6	1	NM_002072.5	ENSP00000286548.4
GNAQ	ENST00000411677.1	c.234+38849G>A		intron_variant	Intron 2 of 3	3		ENSP00000391501.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50963 AN: 151852 Hom.: 10531 Cov.: 31

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.335 AC: 50951 AN: 151968 Hom.: 10525 Cov.: 31 AF XY: 0.334 AC XY: 24778 AN XY: 74242

African (AFR) AF: 0.0976 AC: 4054 AN: 41516

American (AMR) AF: 0.378 AC: 5762 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1337 AN: 3470

East Asian (EAS) AF: 0.182 AC: 938 AN: 5148

South Asian (SAS) AF: 0.314 AC: 1513 AN: 4812

European-Finnish (FIN) AF: 0.468 AC: 4914 AN: 10510

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31085 AN: 67964

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.417 Hom.: 8003

Bravo AF: 0.317

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.17
PhyloP100		-0.19
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: rs4745672; hg19: chr9-80498228;