16-30902524-C-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001330.5(CTF1):ā€‹c.591C>Gā€‹(p.Pro197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,496,536 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0015 ( 0 hom., cov: 31)
Exomes š‘“: 0.0021 ( 3 hom. )

Consequence

CTF1
NM_001330.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.188
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 16-30902524-C-G is Benign according to our data. Variant chr16-30902524-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 44182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.188 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CTF1NM_001330.5 linkuse as main transcriptc.591C>G p.Pro197= synonymous_variant 3/3 ENST00000279804.3 NP_001321.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CTF1ENST00000279804.3 linkuse as main transcriptc.591C>G p.Pro197= synonymous_variant 3/31 NM_001330.5 ENSP00000279804 P3Q16619-1
CTF1ENST00000395019.3 linkuse as main transcriptc.588C>G p.Pro196= synonymous_variant 3/31 ENSP00000378465 A1Q16619-2

Frequencies

GnomAD3 genomes
AF:
0.00153
AC:
232
AN:
152046
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000676
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00354
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00202
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00208
AC:
214
AN:
103072
Hom.:
0
AF XY:
0.00204
AC XY:
119
AN XY:
58380
show subpopulations
Gnomad AFR exome
AF:
0.000766
Gnomad AMR exome
AF:
0.00443
Gnomad ASJ exome
AF:
0.00130
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00268
Gnomad OTH exome
AF:
0.00234
GnomAD4 exome
AF:
0.00213
AC:
2866
AN:
1344380
Hom.:
3
Cov.:
30
AF XY:
0.00212
AC XY:
1402
AN XY:
662670
show subpopulations
Gnomad4 AFR exome
AF:
0.000432
Gnomad4 AMR exome
AF:
0.00436
Gnomad4 ASJ exome
AF:
0.00105
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000131
Gnomad4 FIN exome
AF:
0.000242
Gnomad4 NFE exome
AF:
0.00242
Gnomad4 OTH exome
AF:
0.00194
GnomAD4 genome
AF:
0.00152
AC:
232
AN:
152156
Hom.:
0
Cov.:
31
AF XY:
0.00153
AC XY:
114
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.000674
Gnomad4 AMR
AF:
0.00353
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00202
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.000986
Hom.:
1
Bravo
AF:
0.00182

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineDec 22, 2014p.Pro197Pro in exon 3 of CTF1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.9% (28/3168) of Eur opean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs397516652) -
Benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpOct 15, 2018Variant summary: CTF1 c.591C>G results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0018 in 131558 control chromosomes (gnomAD). The observed variant frequency is approximately 72-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in CTF1 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.591C>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant once as uncertain significance and once as likely benign. Based on the evidence outlined above, the variant was classified as benign. -
Cardiomyopathy Benign:1
Benign, criteria provided, single submitterclinical testingCHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern OntarioMay 04, 2017- -
Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
5.6
DANN
Benign
0.75

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.

Other links and lift over

dbSNP: rs397516652; hg19: chr16-30913845; API