NM_002072.5:c.137-46429A>T

Variant names:

• chr9-77968774-T-A
• rs4745678
• NM_002072.5:c.137-46429A>T

Variant summary

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

The NM_002072.5(GNAQ):​c.137-46429A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,092 control chromosomes in the GnomAD database, including 13,141 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 (13141 hom., cov: 33)
• Consequence: GNAQ NM_002072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• Publications: 2 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

ENSG00000307361 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.475 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.137-46429A>T		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.137-46429A>T		intron	N/A	ENSP00000286548.4	P50148
	GNAQ	ENST00000857199.1		c.212-46429A>T		intron	N/A	ENSP00000527258.1
	GNAQ	ENST00000915940.1		c.137-46429A>T		intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61400 AN: 151974 Hom.: 13141 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.404 AC: 61410 AN: 152092 Hom.: 13141 Cov.: 33 AF XY: 0.402 AC XY: 29900 AN XY: 74344

African (AFR) AF: 0.292 AC: 12114 AN: 41506

American (AMR) AF: 0.484 AC: 7394 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1320 AN: 3462

East Asian (EAS) AF: 0.169 AC: 872 AN: 5166

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4818

European-Finnish (FIN) AF: 0.473 AC: 5003 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31694 AN: 67976

Other (OTH) AF: 0.388 AC: 820 AN: 2112

Alfa AF: 0.283 Hom.: 689

Bravo AF: 0.399

Asia WGS AF: 0.248 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.52
PhyloP100		-0.94
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: rs4745678; hg19: chr9-80583690;