rs73527836

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002067.5(GNA11):c.889+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,612,558 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 Benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

GNA11
NM_002067.5 splice_region, intron

Scores

Splicing: ADA: 0.00003437

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.62

Publications

3 publications found

Variant links:

Genes affected

GNA11 (HGNC:4379): (G protein subunit alpha 11) The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. [provided by RefSeq, Dec 2013]

GNA11 Gene-Disease associations (from GenCC):

autosomal dominant hypocalcemia 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
congenital hemangioma
Inheritance: AD Classification: STRONG Submitted by: G2P
familial hypocalciuric hypercalcemia 2
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal dominant hypocalcemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GNA11 links:

ENSG00000267139 (HGNC:):

ENSG00000267139 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-3119367-G-A is Benign according to our data. Variant chr19-3119367-G-A is described in ClinVar as Benign. ClinVar VariationId is 1170134.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00046 (70/152104) while in subpopulation AFR AF = 0.000579 (24/41444). AF 95% confidence interval is 0.000399. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 70 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002067.5. 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
	GNA11	NM_002067.5	MANE Select	c.889+8G>A		splice_region intron	N/A	NP_002058.2	P29992

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNA11	ENST00000078429.9	TSL:1 MANE Select	c.889+8G>A	splice_region intron	N/A	ENSP00000078429.3	P29992
GNA11	ENST00000587636.1	TSL:5	c.433+8G>A	splice_region intron	N/A	ENSP00000465935.1	K7EL62
GNA11	ENST00000586180.1	TSL:3	n.408+8G>A	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000397

AC:

AN:

249494

AF XY:

0.000333

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00288

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000205

AC:

299

AN:

1460454

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

140

AN XY:

726502

show subpopulations

African (AFR)

AF:

0.000867

AC:

AN:

33466

American (AMR)

AF:

0.0000224

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.000151

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86170

European-Finnish (FIN)

AF:

0.00308

AC:

163

AN:

52998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000576

AC:

AN:

1111304

Other (OTH)

AF:

0.000497

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.000460

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.000579

AC:

AN:

41444

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000387

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.0000621

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

GNA11-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.61

(source)

DANN

Benign

0.83

PhyloP100

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

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