16-30899415-A-C

Variant names:

• chr16-30899415-A-C
• rs2055382034
• NM_001330.5:c.26A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330.5(CTF1):​c.26A>C​(p.Glu9Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTF1 NM_001330.5 missense, splice_region
• Scores: Splicing: ADA: 0.05682
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.82
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17690426).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	NM_001330.5	MANE Select	c.26A>C	p.Glu9Ala	missense splice_region	Exon 2 of 3	NP_001321.1	Q16619-1
	CTF1	NM_001142544.3		c.26-3A>C		splice_region intron	N/A	NP_001136016.1	Q16619-2
	CTF1	NR_165660.1		n.164A>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	ENST00000279804.3	TSL:1 MANE Select	c.26A>C	p.Glu9Ala	missense splice_region	Exon 2 of 3	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.26-3A>C		splice_region intron	N/A	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Dilated Cardiomyopathy, Dominant (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.25
Sift	Benign	0.10	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.61	P
Vest4		0.26
MutPred		0.057		Gain of glycosylation at S7 (P = 0.1124)
MVP		0.85
MPC		0.80
ClinPred		0.48	T
GERP RS		3.7
Varity_R		0.069
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.057
dbscSNV1_RF	Benign	0.47
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2055382034; hg19: chr16-30910736;