6-139372697-G-A

Variant names:

• chr6-139372697-G-A
• rs1131431
• NM_006079.5:c.*435C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006079.5(CITED2):​c.*435C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 223,256 control chromosomes in the GnomAD database, including 8,213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (7020 hom., cov: 32)
  • Exomes 𝑓: 0.16 (1193 hom.)
• Consequence: CITED2 NM_006079.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 15 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
• ventricular septal defect 2

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

ENSG00000226571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	NM_006079.5	MANE Select	c.*435C>T		3_prime_UTR	Exon 2 of 2	NP_006070.2
	CITED2	NM_001168389.3		c.*435C>T		3_prime_UTR	Exon 2 of 2	NP_001161861.2
	CITED2	NM_001168388.3		c.*435C>T		3_prime_UTR	Exon 2 of 2	NP_001161860.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	ENST00000367651.4	TSL:1 MANE Select	c.*435C>T		3_prime_UTR	Exon 2 of 2	ENSP00000356623.2
	CITED2	ENST00000537332.2	TSL:3	c.*435C>T		3_prime_UTR	Exon 2 of 2	ENSP00000444198.2
	CITED2	ENST00000536159.2	TSL:3	c.*435C>T		3_prime_UTR	Exon 2 of 2	ENSP00000442831.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39340 AN: 151976 Hom.: 7012 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.156 AC: 11095 AN: 71162 Hom.: 1193 Cov.: 0 AF XY: 0.152 AC XY: 5783 AN XY: 38100

African (AFR) AF: 0.487 AC: 1190 AN: 2444

American (AMR) AF: 0.127 AC: 518 AN: 4064

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 341 AN: 1652

East Asian (EAS) AF: 0.000448 AC: 2 AN: 4460

South Asian (SAS) AF: 0.107 AC: 1282 AN: 11930

European-Finnish (FIN) AF: 0.169 AC: 508 AN: 3008

Middle Eastern (MID) AF: 0.250 AC: 49 AN: 196

European-Non Finnish (NFE) AF: 0.166 AC: 6665 AN: 40080

Other (OTH) AF: 0.162 AC: 540 AN: 3328

GnomAD4 genome AF: 0.259 AC: 39378 AN: 152094 Hom.: 7020 Cov.: 32 AF XY: 0.253 AC XY: 18773 AN XY: 74330

African (AFR) AF: 0.505 AC: 20923 AN: 41472

American (AMR) AF: 0.159 AC: 2433 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.102 AC: 494 AN: 4830

European-Finnish (FIN) AF: 0.181 AC: 1909 AN: 10550

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12122 AN: 67996

Other (OTH) AF: 0.241 AC: 509 AN: 2110

Alfa AF: 0.201 Hom.: 11806

Bravo AF: 0.270

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1131431; hg19: chr6-139693834;