Variant rs397516649 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000279804.3(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. 12/21 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
ENST00000279804.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0580

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 44179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-30902274-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTF1	NM_001330.5 linkuse as main transcript	c.341G>A	p.Arg114His	missense_variant	3/3	ENST00000279804.3	NP_001321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTF1	ENST00000279804.3 linkuse as main transcript	c.341G>A	p.Arg114His	missense_variant	3/3	1	NM_001330.5	ENSP00000279804	P3	Q16619-1
CTF1	ENST00000395019.3 linkuse as main transcript	c.338G>A	p.Arg113His	missense_variant	3/3	1		ENSP00000378465	A1	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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000249

Gnomad4 OTH exome

AF:

0.0000324

GnomAD4 genome

AF:

0.00000680

AC:

AN:

146996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

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

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 14, 2011

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

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;.

MutationTaster

Benign

0.57

N;N

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over