rs1131431

Positions:

• chr6-139372697-G-A
• chr6-139372697-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000226571 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CITED2	NM_006079.5	c.*435C>T		3_prime_UTR_variant	2/2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168389.3	c.*435C>T		3_prime_UTR_variant	2/2		NP_001161861.2
CITED2	NM_001168388.3	c.*435C>T		3_prime_UTR_variant	2/2		NP_001161860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4	c.*435C>T		3_prime_UTR_variant	2/2	1	NM_006079.5	ENSP00000356623.2
CITED2	ENST00000537332.2	c.*435C>T		3_prime_UTR_variant	2/2	3		ENSP00000444198.2
CITED2	ENST00000536159.2	c.*435C>T		3_prime_UTR_variant	2/2	3		ENSP00000442831.1
ENSG00000226571	ENST00000650173.1	n.510-56384G>A		intron_variant

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

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.000448

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.162

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

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.241

Alfa AF: 0.183 Hom.: 5676

Bravo AF: 0.270

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.88

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: rs1131431; hg19: chr6-139693834;