rs397516649

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001330.5(CTF1):c.341G>A(p.Arg114His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000383 in 1,043,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R114R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

CTF1
NM_001330.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0580

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14565986).

BP6

Variant 16-30902274-G-A is Benign according to our data. Variant chr16-30902274-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 44179.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTF1	NM_001330.5 link	c.341G>A	p.Arg114His	missense_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.341G>A	p.Arg114His	missense_variant	Exon 3 of 3	1	NM_001330.5	ENSP00000279804.2		Q16619-1
CTF1	ENST00000395019.3 link	c.338G>A	p.Arg113His	missense_variant	Exon 3 of 3	1		ENSP00000378465.3		Q16619-2

Frequencies

GnomAD3 genomes

AF:

0.00000680

AC:

AN:

146996

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:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000335

AC:

AN:

896266

Hom.:

Cov.:

AF XY:

0.00000238

AC XY:

AN XY:

420540

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:

17056

American (AMR)

AF:

0.00

AC:

AN:

3486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6976

East Asian (EAS)

AF:

0.00

AC:

AN:

6714

South Asian (SAS)

AF:

0.00

AC:

AN:

18736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1944

European-Non Finnish (NFE)

AF:

0.00000249

AC:

AN:

803900

Other (OTH)

AF:

0.0000324

AC:

AN:

30892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.001100), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000680

AC:

AN:

146996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71510

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40892

American (AMR)

AF:

0.00

AC:

AN:

14826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66064

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 14, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The Arg114His variant has not been previously described in the literature but ha s been detected in 1 Caucasian proband tested by our laboratory. The variant did not segregate with disease in this family and there was no evidence for the pre sence of more than one genetic etiology. Therefore, this variant is more likely benign although a modifying role cannot be excluded. This is consistent with th e lack of evolutionary conservation of arginine (Arg) at position 114 (conserved in mammals but not in more distantly related species) and the predictions of t wo computer tools (Align GVGD, SIFT) although their accuracy is unknown. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Benign

0.0055

Eigen_PC

Benign

-0.045

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.52

T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

-0.058

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.28

Sift

Benign

0.60

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.98

D;.

Vest4

0.18

MutPred

0.31

Loss of MoRF binding (P = 0.0091);.;

MVP

0.79

MPC

1.1

ClinPred

0.39

GERP RS

2.5

Varity_R

0.033

gMVP

0.29

Mutation Taster

=86/14

polymorphism

(source)

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over