dbSNP rs374359365: CTF1:c.144+7G>T (chr16-30899540-G-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001330.5(CTF1):c.144+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,507,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CTF1
NM_001330.5 splice_region, intron

Scores

Splicing: ADA: 0.003689

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00500

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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 16-30899540-G-T is Benign according to our data. Variant chr16-30899540-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 44173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTF1	NM_001330.5 link	c.144+7G>T		splice_region_variant, intron_variant	Intron 2 of 2	ENST00000279804.3	NP_001321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTF1	ENST00000279804.3 link	c.144+7G>T		splice_region_variant, intron_variant	Intron 2 of 2	1	NM_001330.5	ENSP00000279804.2
CTF1	ENST00000395019.3 link	c.141+7G>T		splice_region_variant, intron_variant	Intron 2 of 2	1		ENSP00000378465.3

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000921

AC:

AN:

238882

AF XY:

0.0000693

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000212

AC:

287

AN:

1355370

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

142

AN XY:

675868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30732

American (AMR)

AF:

0.00

AC:

AN:

43356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24862

East Asian (EAS)

AF:

0.00

AC:

AN:

38740

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.000270

AC:

275

AN:

1019374

Other (OTH)

AF:

0.000194

AC:

AN:

56620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000921

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000263

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

144+7G>T in intron 2 of CTF1: This variant is not expected to have clinical sign ificance because it is not located within the splice consensus sequence. It has been identified in 1/8600 European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). 144+7 G>T in intron 2 of CTF1 (allele frequency = 1/8600) ** -

Dilated Cardiomyopathy, Dominant

Benign:1

Jun 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.6

(source)

DANN

Benign

0.79

PhyloP100

0.0050

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0037

dbscSNV1_RF

Benign

0.10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over