16-30902213-C-G

Variant names:

• chr16-30902213-C-G
• rs397516648
• NM_001330.5:c.280C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330.5(CTF1):​c.280C>G​(p.Leu94Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000989 in 1,011,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L94L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: CTF1 NM_001330.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40194255).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	NM_001330.5	MANE Select	c.280C>G	p.Leu94Val	missense	Exon 3 of 3	NP_001321.1
	CTF1	NM_001142544.3		c.277C>G	p.Leu93Val	missense	Exon 3 of 3	NP_001136016.1
	CTF1	NR_165660.1		n.418C>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	ENST00000279804.3	TSL:1 MANE Select	c.280C>G	p.Leu94Val	missense	Exon 3 of 3	ENSP00000279804.2
	CTF1	ENST00000395019.3	TSL:1	c.277C>G	p.Leu93Val	missense	Exon 3 of 3	ENSP00000378465.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.89e-7 AC: 1 AN: 1011192 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 477778

African (AFR) AF: 0.00 AC: 0 AN: 20248

American (AMR) AF: 0.00 AC: 0 AN: 5996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10986

East Asian (EAS) AF: 0.00 AC: 0 AN: 19364

South Asian (SAS) AF: 0.00 AC: 0 AN: 19200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 877290

Other (OTH) AF: 0.0000261 AC: 1 AN: 38336

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.0021
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.74
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.42
Sift	Uncertain	0.017	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.46		Gain of helix (P = 0.2059)
MVP		0.83
MPC		1.1
ClinPred		0.52	D
GERP RS		3.9
Varity_R		0.20
gMVP		0.33

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

Other links and lift over

dbSNP: rs397516648; hg19: chr16-30913534;