dbSNP rs541676373: GNAQ:c.736-5T>C (chr9-77728672-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002072.5(GNAQ):c.736-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000486 in 782,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

GNAQ
NM_002072.5 splice_region, intron

Scores

Splicing: ADA: 0.00005036

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.572

Publications

1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

GNAQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-77728672-A-G is Benign according to our data. Variant chr9-77728672-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3057817.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 12 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.736-5T>C		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.736-5T>C	splice_region intron	N/A	ENSP00000286548.4	P50148
GNAQ	ENST00000857199.1		c.811-5T>C	splice_region intron	N/A	ENSP00000527258.1
GNAQ	ENST00000915940.1		c.736-5T>C	splice_region intron	N/A	ENSP00000585999.1

Frequencies

GnomAD3 genomes

AF:

0.000614

AC:

AN:

19530

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000640

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000172

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000952

AC:

AN:

35714

AF XY:

0.000893

show subpopulations

Gnomad AFR exome

AF:

0.00202

Gnomad AMR exome

AF:

0.00164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000746

Gnomad FIN exome

AF:

0.000637

Gnomad NFE exome

AF:

0.000847

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000341

AC:

AN:

763060

Hom.:

Cov.:

AF XY:

0.0000397

AC XY:

AN XY:

377780

show subpopulations

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

African (AFR)

AF:

0.000349

AC:

AN:

11458

American (AMR)

AF:

0.00

AC:

AN:

16742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11918

East Asian (EAS)

AF:

0.000328

AC:

AN:

15244

South Asian (SAS)

AF:

0.0000271

AC:

AN:

36888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3232

European-Non Finnish (NFE)

AF:

0.0000212

AC:

AN:

612138

Other (OTH)

AF:

0.000100

AC:

AN:

29874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000784595), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.335

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000614

AC:

AN:

19558

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

AN XY:

9692

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

8270

American (AMR)

AF:

0.00

AC:

AN:

1438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

380

East Asian (EAS)

AF:

0.000639

AC:

AN:

1564

South Asian (SAS)

AF:

0.00

AC:

AN:

740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000172

AC:

AN:

5812

Other (OTH)

AF:

0.00

AC:

AN:

266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

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:

0.0000284

Hom.:

Bravo

AF:

0.0000567

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GNAQ-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.43

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000050

dbscSNV1_RF

Benign

0.0060

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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