Genetic Variant CTF1:p.Ala138Ala (chr16-30902347-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001330.5(CTF1):c.414C>T(p.Ala138Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 980,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A138A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

CTF1
NM_001330.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Publications

0 publications found

Variant links:

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

CTF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=0.038 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTF1	NM_001330.5 link	c.414C>T	p.Ala138Ala	synonymous_variant	Exon 3 of 3	ENST00000279804.3	NP_001321.1	Q16619-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTF1	ENST00000279804.3 link	c.414C>T	p.Ala138Ala	synonymous_variant	Exon 3 of 3	1	NM_001330.5	ENSP00000279804.2		Q16619-1
CTF1	ENST00000395019.3 link	c.411C>T	p.Ala137Ala	synonymous_variant	Exon 3 of 3	1		ENSP00000378465.3		Q16619-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000102

AC:

AN:

980052

Hom.:

Cov.:

AF XY:

0.00000216

AC XY:

AN XY:

463568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19182

American (AMR)

AF:

0.00

AC:

AN:

5044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9738

East Asian (EAS)

AF:

0.00

AC:

AN:

16660

South Asian (SAS)

AF:

0.00

AC:

AN:

19678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2372

European-Non Finnish (NFE)

AF:

0.00000117

AC:

AN:

857774

Other (OTH)

AF:

0.00

AC:

AN:

36046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.3

(source)

DANN

Benign

0.88

PhyloP100

0.038

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over