Variant 6-139373435-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006079.5(CITED2):c.510G>C(p.Ser170=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,519,228 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 6 hom. )

Consequence

CITED2
NM_006079.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.749

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 6-139373435-C-G is Benign according to our data. Variant chr6-139373435-C-G is described in ClinVar as [Benign]. Clinvar id is 776166.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.749 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00652 (986/151286) while in subpopulation AFR AF= 0.0228 (939/41244). AF 95% confidence interval is 0.0216. There are 14 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CITED2	NM_006079.5 linkuse as main transcript	c.510G>C	p.Ser170=	synonymous_variant	2/2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168389.3 linkuse as main transcript	c.525G>C	p.Ser175=	synonymous_variant	2/2		NP_001161861.2
CITED2	NM_001168388.3 linkuse as main transcript	c.510G>C	p.Ser170=	synonymous_variant	2/2		NP_001161860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4 linkuse as main transcript	c.510G>C	p.Ser170=	synonymous_variant	2/2	1	NM_006079.5	ENSP00000356623	P1	Q99967-1
	ENST00000650173.1 linkuse as main transcript	n.510-55646C>G		intron_variant, non_coding_transcript_variant
CITED2	ENST00000537332.2 linkuse as main transcript	c.525G>C	p.Ser175=	synonymous_variant	2/2	3		ENSP00000444198
CITED2	ENST00000536159.2 linkuse as main transcript	c.510G>C	p.Ser170=	synonymous_variant	2/2	3		ENSP00000442831	P1	Q99967-1

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

985

AN:

151178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00198

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:

0.0000885

Gnomad OTH

AF:

0.00531

GnomAD3 exomes

AF:

0.00172

AC:

295

AN:

171940

Hom.:

AF XY:

0.00119

AC XY:

113

AN XY:

94572

show subpopulations

Gnomad AFR exome

AF:

0.0225

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:

0.0000606

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000695

AC:

951

AN:

1367942

Hom.:

Cov.:

AF XY:

0.000625

AC XY:

423

AN XY:

677198

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00162

Gnomad4 ASJ exome

AF:

0.0000477

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000426

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000701

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00652

AC:

986

AN:

151286

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

454

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000885

Gnomad4 OTH

AF:

0.00526

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.00768

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.4

DANN

Benign

0.82

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