6-139373403-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_006079.5(CITED2):c.542G>C(p.Ser181Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000272 in 1,545,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

CITED2
NM_006079.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.108

Variant links:

Genes affected

CITED2 (HGNC:1987): (Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2) The protein encoded by this gene inhibits transactivation of HIF1A-induced genes by competing with binding of hypoxia-inducible factor 1-alpha to p300-CH1. Mutations in this gene are a cause of cardiac septal defects. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CITED2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07755205).

BP6

Variant 6-139373403-C-G is Benign according to our data. Variant chr6-139373403-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1174691.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-139373403-C-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAdExome at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CITED2	NM_006079.5 linkuse as main transcript	c.542G>C	p.Ser181Thr	missense_variant	2/2	ENST00000367651.4
CITED2	NM_001168389.3 linkuse as main transcript	c.557G>C	p.Ser186Thr	missense_variant	2/2
CITED2	NM_001168388.3 linkuse as main transcript	c.542G>C	p.Ser181Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CITED2	ENST00000367651.4 linkuse as main transcript	c.542G>C	p.Ser181Thr	missense_variant	2/2	1	NM_006079.5	P1	Q99967-1
	ENST00000650173.1 linkuse as main transcript	n.510-55678C>G		intron_variant, non_coding_transcript_variant
CITED2	ENST00000537332.2 linkuse as main transcript	c.557G>C	p.Ser186Thr	missense_variant	2/2	3
CITED2	ENST00000536159.2 linkuse as main transcript	c.542G>C	p.Ser181Thr	missense_variant	2/2	3		P1	Q99967-1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

183372

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

102830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000701

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000272

AC:

AN:

1394732

Hom.:

Cov.:

AF XY:

0.0000231

AC XY:

AN XY:

693102

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.0000323

Gnomad4 OTH exome

AF:

0.0000349

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151250

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73848

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000850

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.78

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.077

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.078

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.14

N;.;N

REVEL

Benign

0.10

Sift

Benign

0.48

T;.;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.21

MutPred

0.36

Loss of phosphorylation at S181 (P = 0.0738);.;Loss of phosphorylation at S181 (P = 0.0738);

MVP

0.48

MPC

0.28

ClinPred

0.025

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.48

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