Genetic Variant CTF1:p.Leu94Leu (chr16-30902215-G-A) – 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.282G>A(p.Leu94Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 1,159,904 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. L94L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 9.9e-7 ( 0 hom. )

Consequence

CTF1
NM_001330.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839

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

new If you want to explore the variant's impact on the transcript NM_001330.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.63).

BP7

Synonymous conserved (PhyloP=-0.839 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTF1	NM_001330.5	MANE Select	c.282G>A	p.Leu94Leu	synonymous	Exon 3 of 3	NP_001321.1	Q16619-1
CTF1	NM_001142544.3		c.279G>A	p.Leu93Leu	synonymous	Exon 3 of 3	NP_001136016.1	Q16619-2
CTF1	NR_165660.1		n.420G>A		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.282G>A	p.Leu94Leu	synonymous	Exon 3 of 3	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.279G>A	p.Leu93Leu	synonymous	Exon 3 of 3	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.89e-7

AC:

AN:

1011018

Hom.:

Cov.:

AF XY:

0.00000209

AC XY:

AN XY:

477674

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

20252

American (AMR)

AF:

0.00

AC:

AN:

6002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10968

East Asian (EAS)

AF:

0.00

AC:

AN:

19356

South Asian (SAS)

AF:

0.00

AC:

AN:

19190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2520

European-Non Finnish (NFE)

AF:

0.00000114

AC:

AN:

877166

Other (OTH)

AF:

0.00

AC:

AN:

38328

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72574

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41080

American (AMR)

AF:

0.00

AC:

AN:

15000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66834

Other (OTH)

AF:

0.00

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.8

(source)

DANN

Benign

0.92

PhyloP100

-0.84

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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over