16-30902270-CCG-CCGCG

Variant names:

• chr16-30902270-C-CCG
• rs1167643962
• NM_001330.5:c.345_346dupGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001330.5(CTF1):​c.345_346dupGC​(p.Pro116ArgfsTer71) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 896,442 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CTF1 NM_001330.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.394
• Publications: 0 publications found

Genes affected

CTF1 (HGNC:2499): (cardiotrophin 1) The protein encoded by this gene is a secreted cytokine that induces cardiac myocyte hypertrophy in vitro. It has been shown to bind and activate the ILST/gp130 receoptor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

CTF1 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330.5. 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
	CTF1	NM_001330.5	MANE Select	c.345_346dupGC	p.Pro116ArgfsTer71	frameshift	Exon 3 of 3	NP_001321.1	Q16619-1
	CTF1	NM_001142544.3		c.342_343dupGC	p.Pro115ArgfsTer71	frameshift	Exon 3 of 3	NP_001136016.1	Q16619-2
	CTF1	NR_165660.1		n.483_484dupGC		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	ENST00000279804.3	TSL:1 MANE Select	c.345_346dupGC	p.Pro116ArgfsTer71	frameshift	Exon 3 of 3	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.342_343dupGC	p.Pro115ArgfsTer71	frameshift	Exon 3 of 3	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000223 AC: 2 AN: 896442 Hom.: 0 Cov.: 30 AF XY: 0.00000475 AC XY: 2 AN XY: 420640

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17060

American (AMR) AF: 0.00 AC: 0 AN: 3510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6976

East Asian (EAS) AF: 0.00 AC: 0 AN: 6740

South Asian (SAS) AF: 0.0000534 AC: 1 AN: 18732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1944

European-Non Finnish (NFE) AF: 0.00000124 AC: 1 AN: 803992

Other (OTH) AF: 0.00 AC: 0 AN: 30906

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Dilated Cardiomyopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39

Splicing

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

Other links and lift over

dbSNP: rs1167643962; hg19: chr16-30913591;