6-139373435-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.749

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]

(HGNC:):

ACMG classification

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 GnomAd at 985 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CITED2	NM_006079.5	c.510G>C	p.Ser170=	synonymous_variant	2/2	ENST00000367651.4
CITED2	NM_001168389.3	c.525G>C	p.Ser175=	synonymous_variant	2/2
CITED2	NM_001168388.3	c.510G>C	p.Ser170=	synonymous_variant	2/2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 985 AN: 151178 Hom.: 14 Cov.: 32

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.: 2 AF XY: 0.00119 AC XY: 113 AN XY: 94572

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.: 6 Cov.: 30 AF XY: 0.000625 AC XY: 423 AN XY: 677198

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.: 14 Cov.: 32 AF XY: 0.00614 AC XY: 454 AN XY: 73962

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.: 0

Bravo AF: 0.00768

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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

Other links and lift over

dbSNP: rs139128813; hg19: chr6-139694572;