6-139373318-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006079.5(CITED2):​c.627C>T​(p.Pro209Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,612,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

CITED2
NM_006079.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.120
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 6-139373318-G-A is Benign according to our data. Variant chr6-139373318-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 733119.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.12 with no splicing effect.
BS2
High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CITED2NM_006079.5 linkc.627C>T p.Pro209Pro synonymous_variant Exon 2 of 2 ENST00000367651.4 NP_006070.2 Q99967-1D9ZGF1
CITED2NM_001168389.3 linkc.642C>T p.Pro214Pro synonymous_variant Exon 2 of 2 NP_001161861.2 Q99967A0A0A0MTM3
CITED2NM_001168388.3 linkc.627C>T p.Pro209Pro synonymous_variant Exon 2 of 2 NP_001161860.1 Q99967-1D9ZGF1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CITED2ENST00000367651.4 linkc.627C>T p.Pro209Pro synonymous_variant Exon 2 of 2 1 NM_006079.5 ENSP00000356623.2 Q99967-1
CITED2ENST00000537332.2 linkc.642C>T p.Pro214Pro synonymous_variant Exon 2 of 2 3 ENSP00000444198.2 A0A0A0MTM3
CITED2ENST00000536159.2 linkc.627C>T p.Pro209Pro synonymous_variant Exon 2 of 2 3 ENSP00000442831.1 Q99967-1
ENSG00000226571ENST00000650173.1 linkn.510-55763G>A intron_variant Intron 4 of 7

Frequencies

GnomAD3 genomes
AF:
0.000329
AC:
50
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00308
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000211
AC:
51
AN:
242004
Hom.:
0
AF XY:
0.000189
AC XY:
25
AN XY:
132152
show subpopulations
Gnomad AFR exome
AF:
0.0000649
Gnomad AMR exome
AF:
0.00134
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:
0.0000375
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000582
AC:
85
AN:
1460606
Hom.:
0
Cov.:
31
AF XY:
0.0000619
AC XY:
45
AN XY:
726618
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00154
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000329
AC:
50
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.000484
AC XY:
36
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00308
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000416

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 23, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
7.4
DANN
Benign
0.93

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.

Other links and lift over

dbSNP: rs767902739; hg19: chr6-139694455; API