Variant 7-2814361-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_007353.3(GNA12):c.310-19218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 1,603,128 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0079 ( 70 hom. )

Consequence

GNA12
NM_007353.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.109

Variant links:

Genes affected

GNA12 (HGNC:4380): (G protein subunit alpha 12) Predicted to enable D5 dopamine receptor binding activity; G-protein beta/gamma-subunit complex binding activity; and GTPase activity. Involved in regulation of TOR signaling and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

GNA12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004283428).

BP6

Variant 7-2814361-C-T is Benign according to our data. Variant chr7-2814361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657237.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00793 (11507/1451118) while in subpopulation MID AF= 0.0254 (146/5744). AF 95% confidence interval is 0.0221. There are 70 homozygotes in gnomad4_exome. There are 5671 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High AC in GnomAd4 at 904 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GNA12	NM_007353.3 linkuse as main transcript	c.310-19218G>A		intron_variant		ENST00000275364.8
GNA12	NM_001282441.2 linkuse as main transcript	c.83G>A	p.Arg28Gln	missense_variant	2/5
GNA12	NM_001293092.2 linkuse as main transcript	c.310-19218G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8 linkuse as main transcript	c.310-19218G>A		intron_variant		1	NM_007353.3	P1	Q03113-1
GNA12	ENST00000407904.7 linkuse as main transcript	c.83G>A	p.Arg28Gln	missense_variant	2/5	2			Q03113-2
GNA12	ENST00000447791.1 linkuse as main transcript	c.54+516G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00594

AC:

902

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00617

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00956

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00607

AC:

1467

AN:

241542

Hom.:

AF XY:

0.00655

AC XY:

869

AN XY:

132636

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.00366

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00273

Gnomad FIN exome

AF:

0.000975

Gnomad NFE exome

AF:

0.00998

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00793

AC:

11507

AN:

1451118

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

5671

AN XY:

722500

show subpopulations

Gnomad4 AFR exome

AF:

0.00192

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00305

Gnomad4 FIN exome

AF:

0.000937

Gnomad4 NFE exome

AF:

0.00909

Gnomad4 OTH exome

AF:

0.00831

GnomAD4 genome

AF:

0.00595

AC:

904

AN:

152010

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

433

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00616

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00375

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00956

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00806

Hom.:

Bravo

AF:

0.00640

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00171

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00639

AC:

741

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0114

EpiControl

AF:

0.0120

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

GNA12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.52

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

1.2

REVEL

Benign

0.17

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.014

Vest4

0.12

MVP

0.47

ClinPred

0.0030

GERP RS

2.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over