rs139128813

Variant names:

• chr6-139373435-C-G
• rs139128813
• NM_006079.5:c.510G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-139373435-C-G
• chr6-139373435-C-A
• chr6-139373435-C-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_006079.5(CITED2):​c.510G>C​(p.Ser170Ser) 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• atrial septal defect 8

  Inheritance: AD Classification: MODERATE Submitted by: Laboratory for Molecular Medicine
• congenital heart defects, multiple types

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• ventricular septal defect 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000226571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 986 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	NM_006079.5	MANE Select	c.510G>C	p.Ser170Ser	synonymous	Exon 2 of 2	NP_006070.2
	CITED2	NM_001168389.3		c.525G>C	p.Ser175Ser	synonymous	Exon 2 of 2	NP_001161861.2	A0A0A0MTM3
	CITED2	NM_001168388.3		c.510G>C	p.Ser170Ser	synonymous	Exon 2 of 2	NP_001161860.1	Q99967-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	ENST00000367651.4	TSL:1 MANE Select	c.510G>C	p.Ser170Ser	synonymous	Exon 2 of 2	ENSP00000356623.2	Q99967-1
	CITED2	ENST00000537332.2	TSL:3	c.525G>C	p.Ser175Ser	synonymous	Exon 2 of 2	ENSP00000444198.2	A0A0A0MTM3
	CITED2	ENST00000536159.2	TSL:3	c.510G>C	p.Ser170Ser	synonymous	Exon 2 of 2	ENSP00000442831.1	Q99967-1

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

GnomAD2 exomes AF: 0.00172 AC: 295 AN: 171940 AF XY: 0.00119

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 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

African (AFR) AF: 0.0247 AC: 726 AN: 29368

American (AMR) AF: 0.00162 AC: 52 AN: 32086

Ashkenazi Jewish (ASJ) AF: 0.0000477 AC: 1 AN: 20964

East Asian (EAS) AF: 0.00 AC: 0 AN: 35380

South Asian (SAS) AF: 0.0000426 AC: 3 AN: 70360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48122

Middle Eastern (MID) AF: 0.00150 AC: 8 AN: 5342

European-Non Finnish (NFE) AF: 0.0000701 AC: 75 AN: 1070078

Other (OTH) AF: 0.00153 AC: 86 AN: 56242

GnomAD4 genome AF: 0.00652 AC: 986 AN: 151286 Hom.: 14 Cov.: 32 AF XY: 0.00614 AC XY: 454 AN XY: 73962

African (AFR) AF: 0.0228 AC: 939 AN: 41244

American (AMR) AF: 0.00198 AC: 30 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000885 AC: 6 AN: 67786

Other (OTH) AF: 0.00526 AC: 11 AN: 2090

Alfa AF: 0.000280 Hom.: 0

Bravo AF: 0.00768

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs139128813; hg19: chr6-139694572;