dbSNP rs727505121: CTF1:p.Ala138Ala (chr16-30902347-C-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001330.5(CTF1):c.414C>A(p.Ala138Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,127,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CTF1
NM_001330.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0380

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 16-30902347-C-A is Benign according to our data. Variant chr16-30902347-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 179780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.038 with no splicing effect.

BS2

High AC in GnomAd4 at 5 AD gene.

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.414C>A	p.Ala138Ala	synonymous	Exon 3 of 3	NP_001321.1	Q16619-1
CTF1	NM_001142544.3		c.411C>A	p.Ala137Ala	synonymous	Exon 3 of 3	NP_001136016.1	Q16619-2
CTF1	NR_165660.1		n.552C>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.414C>A	p.Ala138Ala	synonymous	Exon 3 of 3	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.411C>A	p.Ala137Ala	synonymous	Exon 3 of 3	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes

AF:

0.0000338

AC:

AN:

147900

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:

0.0000751

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

980052

Hom.:

Cov.:

AF XY:

0.0000173

AC XY:

AN XY:

463568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19182

American (AMR)

AF:

0.00

AC:

AN:

5044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9738

East Asian (EAS)

AF:

0.00

AC:

AN:

16660

South Asian (SAS)

AF:

0.00

AC:

AN:

19678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2372

European-Non Finnish (NFE)

AF:

0.0000140

AC:

AN:

857774

Other (OTH)

AF:

0.0000277

AC:

AN:

36046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000338

AC:

AN:

147900

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40980

American (AMR)

AF:

0.00

AC:

AN:

14882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3414

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000751

AC:

AN:

66584

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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:

0.0000712

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dilated Cardiomyopathy, Dominant (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.7

(source)

DANN

Benign

0.77

PhyloP100

0.038

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over