NM_001330.5:c.347C>T

Variant names:

• chr16-30902280-C-T
• rs886051924
• NM_001330.5:c.347C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001330.5(CTF1):​c.347C>T​(p.Pro116Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000388 in 1,031,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P116R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CTF1 NM_001330.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.69
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039742887).

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.347C>T	p.Pro116Leu	missense	Exon 3 of 3	NP_001321.1	Q16619-1
	CTF1	NM_001142544.3		c.344C>T	p.Pro115Leu	missense	Exon 3 of 3	NP_001136016.1	Q16619-2
	CTF1	NR_165660.1		n.485C>T		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.347C>T	p.Pro116Leu	missense	Exon 3 of 3	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.344C>T	p.Pro115Leu	missense	Exon 3 of 3	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 146964 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000226 AC: 2 AN: 884346 Hom.: 0 Cov.: 30 AF XY: 0.00000483 AC XY: 2 AN XY: 414282

African (AFR) AF: 0.00 AC: 0 AN: 16802

American (AMR) AF: 0.00 AC: 0 AN: 3112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6626

East Asian (EAS) AF: 0.000345 AC: 2 AN: 5794

South Asian (SAS) AF: 0.00 AC: 0 AN: 18586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1878

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 796144

Other (OTH) AF: 0.00 AC: 0 AN: 30126

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 146964 Hom.: 0 Cov.: 31 AF XY: 0.0000140 AC XY: 1 AN XY: 71508

African (AFR) AF: 0.0000244 AC: 1 AN: 40940

American (AMR) AF: 0.00 AC: 0 AN: 14808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66038

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Dilated Cardiomyopathy, Dominant (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.4
DANN	Benign	0.95
DEOGEN2	Uncertain	0.72	D
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.95	L
PhyloP100		-1.7
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Benign	0.086	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.052
MutPred		0.29		Loss of loop (P = 0.0128)
MVP		0.60
MPC		0.43
ClinPred		0.16	T
GERP RS		-6.5
Varity_R		0.052
gMVP		0.31
Mutation Taster		=94/6	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: rs886051924; hg19: chr16-30913601;