chr16-30899491-G-C

Variant names:

• chr16-30899491-G-C
• rs727504837
• NM_001330.5:c.102G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001330.5(CTF1):​c.102G>C​(p.Ala34Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A34A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CTF1 NM_001330.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.

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.102G>C	p.Ala34Ala	synonymous	Exon 2 of 3	NP_001321.1
	CTF1	NM_001142544.3		c.99G>C	p.Ala33Ala	synonymous	Exon 2 of 3	NP_001136016.1
	CTF1	NR_165660.1		n.240G>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	ENST00000279804.3	TSL:1 MANE Select	c.102G>C	p.Ala34Ala	synonymous	Exon 2 of 3	ENSP00000279804.2
	CTF1	ENST00000395019.3	TSL:1	c.99G>C	p.Ala33Ala	synonymous	Exon 2 of 3	ENSP00000378465.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.9
DANN	Benign	0.71
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs727504837; hg19: chr16-30910812;