16-30902274-G-C

Variant names:

• chr16-30902274-G-C
• NM_001330.5:c.341G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330.5(CTF1):​c.341G>C​(p.Arg114Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000112 in 896,266 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R114H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: CTF1 NM_001330.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19381234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTF1	NM_001330.5	c.341G>C	p.Arg114Pro	missense_variant	Exon 3 of 3	ENST00000279804.3	NP_001321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTF1	ENST00000279804.3	c.341G>C	p.Arg114Pro	missense_variant	Exon 3 of 3	1	NM_001330.5	ENSP00000279804.2
CTF1	ENST00000395019.3	c.338G>C	p.Arg113Pro	missense_variant	Exon 3 of 3	1		ENSP00000378465.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000112 AC: 1 AN: 896266 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 420540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000124

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.0060	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	0.071
Eigen_PC	Benign	0.0015
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.49	T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.51	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.32	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.99	D;.
Vest4		0.17
MutPred		0.30		Loss of MoRF binding (P = 4e-04);.;
MVP		0.76
MPC		1.2
ClinPred		0.59	D
GERP RS		2.5
Varity_R		0.15
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-30913595;