16-30902065-C-T

Variant names:

• chr16-30902065-C-T
• rs397516646
• NM_001330.5:c.145-13C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001330.5(CTF1):​c.145-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000511 in 1,448,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: CTF1 NM_001330.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.549
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 16-30902065-C-T is Benign according to our data. Variant chr16-30902065-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 44175.
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTF1	NM_001330.5	c.145-13C>T		intron_variant	Intron 2 of 2	ENST00000279804.3	NP_001321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTF1	ENST00000279804.3	c.145-13C>T		intron_variant	Intron 2 of 2	1	NM_001330.5	ENSP00000279804.2
CTF1	ENST00000395019.3	c.142-13C>T		intron_variant	Intron 2 of 2	1		ENSP00000378465.3

Frequencies

GnomAD3 genomes AF: 0.0000922 AC: 14 AN: 151898 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.000122 AC: 10 AN: 82004 AF XY: 0.000128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000181

Gnomad ASJ exome AF: 0.000756

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000682

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000463 AC: 60 AN: 1296604 Hom.: 0 Cov.: 30 AF XY: 0.0000454 AC XY: 29 AN XY: 639366

African (AFR) AF: 0.0000751 AC: 2 AN: 26624

American (AMR) AF: 0.000180 AC: 5 AN: 27848

Ashkenazi Jewish (ASJ) AF: 0.00102 AC: 23 AN: 22504

East Asian (EAS) AF: 0.00 AC: 0 AN: 29034

South Asian (SAS) AF: 0.00 AC: 0 AN: 71034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30936

Middle Eastern (MID) AF: 0.000266 AC: 1 AN: 3760

European-Non Finnish (NFE) AF: 0.0000174 AC: 18 AN: 1031836

Other (OTH) AF: 0.000207 AC: 11 AN: 53028

GnomAD4 genome AF: 0.0000922 AC: 14 AN: 151898 Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7 AN XY: 74206

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.000196 AC: 3 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10458

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000349 Hom.: 0

Bravo AF: 0.0000491

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Apr 27, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 145-13C>T variant (CTF1) has not been reported in the literature nor previou sly identified by our laboratory. This variant is located in the 3' splice regio n. Computational tools do not predict altered splicing; however, this informatio n is not predictive enough to rule out pathogenicity. Additional studies are nee ded to fully assess the clinical significance of the 145-13C>T variant. -

Dilated Cardiomyopathy, Dominant Benign:1

Oct 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		0.55

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: rs397516646; hg19: chr16-30913386;