Genetic Variant GNAQ:c.736-6_736-5dupTT (chr9-77728671-G-GAA) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_002072.5(GNAQ):c.736-6_736-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 1,298,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.049 ( 0 hom. )

Consequence

GNAQ
NM_002072.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: -0.572

Publications

5 publications found

Variant links:

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

GNAQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 9-77728671-G-GAA is Benign according to our data. Variant chr9-77728671-G-GAA is described in ClinVar as Benign. ClinVar VariationId is 770953.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 208 AD gene.

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.736-6_736-5dupTT		splice_region intron	N/A	NP_002063.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNAQ	ENST00000286548.9	TSL:1 MANE Select	c.736-5_736-4insTT	splice_region intron	N/A	ENSP00000286548.4	P50148
GNAQ	ENST00000857199.1		c.811-5_811-4insTT	splice_region intron	N/A	ENSP00000527258.1
GNAQ	ENST00000915940.1		c.736-5_736-4insTT	splice_region intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

207

AN:

145514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00143

Gnomad ASJ

AF:

0.000585

Gnomad EAS

AF:

0.00303

Gnomad SAS

AF:

0.000647

Gnomad FIN

AF:

0.00391

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00151

GnomAD2 exomes

AF:

0.0249

AC:

4251

AN:

170990

AF XY:

0.0248

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.0299

Gnomad ASJ exome

AF:

0.0339

Gnomad EAS exome

AF:

0.0178

Gnomad FIN exome

AF:

0.0238

Gnomad NFE exome

AF:

0.0250

Gnomad OTH exome

AF:

0.0329

GnomAD4 exome

AF:

0.0493

AC:

56832

AN:

1153140

Hom.:

Cov.:

AF XY:

0.0482

AC XY:

27878

AN XY:

578696

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0252

AC:

669

AN:

26580

American (AMR)

AF:

0.0331

AC:

952

AN:

28736

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

814

AN:

20778

East Asian (EAS)

AF:

0.0243

AC:

872

AN:

35896

South Asian (SAS)

AF:

0.0406

AC:

2795

AN:

68776

European-Finnish (FIN)

AF:

0.0344

AC:

1440

AN:

41814

Middle Eastern (MID)

AF:

0.0360

AC:

161

AN:

4468

European-Non Finnish (NFE)

AF:

0.0535

AC:

46969

AN:

877414

Other (OTH)

AF:

0.0444

AC:

2160

AN:

48678

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.284

Heterozygous variant carriers

4475

8950

13426

17901

22376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

1874

3748

5622

7496

9370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00143

AC:

208

AN:

145580

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

109

AN XY:

70566

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

39610

American (AMR)

AF:

0.00143

AC:

AN:

14682

Ashkenazi Jewish (ASJ)

AF:

0.000585

AC:

AN:

3420

East Asian (EAS)

AF:

0.00304

AC:

AN:

4934

South Asian (SAS)

AF:

0.000650

AC:

AN:

4616

European-Finnish (FIN)

AF:

0.00391

AC:

AN:

8702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

66428

Other (OTH)

AF:

0.00150

AC:

AN:

2006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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9-77728671-GAAAAA-GAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over