Variant chr12-56276015-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_004077.3(CS):c.769C>T(p.Leu257=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0122 in 1,614,172 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 8 hom., cov: 31)

Exomes 𝑓: 0.013 ( 176 hom. )

Consequence

CS
NM_004077.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.89

Variant links:

Genes affected

CS (HGNC:2422): (citrate synthase) The protein encoded by this gene is a Krebs tricarboxylic acid cycle enzyme that catalyzes the synthesis of citrate from oxaloacetate and acetyl coenzyme A. The enzyme is found in nearly all cells capable of oxidative metablism. This protein is nuclear encoded and transported into the mitochondrial matrix, where the mature form is found. [provided by RefSeq, Jul 2008]

CS 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 (BayesDel_noAF=-0.41).

BP6

Variant 12-56276015-G-A is Benign according to our data. Variant chr12-56276015-G-A is described in ClinVar as [Benign]. Clinvar id is 777689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CS	NM_004077.3 linkuse as main transcript	c.769C>T	p.Leu257=	synonymous_variant	7/11	ENST00000351328.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CS	ENST00000351328.8 linkuse as main transcript	c.769C>T	p.Leu257=	synonymous_variant	7/11	1	NM_004077.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00892

AC:

1358

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00914

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00797

AC:

2003

AN:

251384

Hom.:

AF XY:

0.00787

AC XY:

1069

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.00775

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00841

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.0126

AC:

18367

AN:

1461876

Hom.:

176

Cov.:

AF XY:

0.0120

AC XY:

8762

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00879

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.00768

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.00892

AC:

1359

AN:

152296

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00914

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00982

Hom.:

Bravo

AF:

0.00849

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.2

DANN

Benign

0.73

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

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