3-184383572-CC-TT

Variant names:

• chr3-184383572-CC-TT
• NM_003741.4:c.1370_1371delCCinsTT
• CHRD p.Thr457Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003741.4(CHRD):​c.1370_1371delCCinsTT​(p.Thr457Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T457S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRD NM_003741.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• Publications: 0 publications found

Genes affected

CHRD (HGNC:1949): (chordin) This gene encodes a secreted protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta-like bone morphogenetic proteins and sequestering them in latent complexes. The encoded protein may also have roles in organogenesis and during adulthood. It has been suggested that this gene could be a candidate gene for Cornelia de Lange syndrome. Reduced expression of this gene results in enhanced bone regeneration. Alternative splicing results in multiple transcript variants. Other alternative splice variants have been described but their full length sequence has not been determined. [provided by RefSeq, Jan 2015]

CHRD Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003741.4. 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
	CHRD	NM_003741.4	MANE Select	c.1370_1371delCCinsTT	p.Thr457Ile	missense	N/A	NP_003732.2
	CHRD	NM_001304472.2		c.1370_1371delCCinsTT	p.Thr457Ile	missense	N/A	NP_001291401.1	E7ESX1
	CHRD	NM_001304473.2		c.260_261delCCinsTT	p.Thr87Ile	missense	N/A	NP_001291402.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRD	ENST00000204604.6	TSL:1 MANE Select	c.1370_1371delCCinsTT	p.Thr457Ile	missense	N/A	ENSP00000204604.1	Q9H2X0-1
	CHRD	ENST00000450923.5	TSL:1	c.1370_1371delCCinsTT	p.Thr457Ile	missense	N/A	ENSP00000408972.1	E7ESX1
	CHRD	ENST00000420973.5	TSL:1	n.*288_*289delCCinsTT		non_coding_transcript_exon	Exon 12 of 23	ENSP00000392794.1	Q9H2X0-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-184101360;