rs727502950

Variant names:

• chr16-30902252-C-A
• rs727502950
• NM_001330.5:c.319C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-30902252-C-A
• chr16-30902252-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001330.5(CTF1):​c.319C>A​(p.Arg107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000542 in 1,106,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: CTF1 NM_001330.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.0520
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15795329).
• BS2: High AC in GnomAdExome4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	NM_001330.5	MANE Select	c.319C>A	p.Arg107Ser	missense	Exon 3 of 3	NP_001321.1	Q16619-1
	CTF1	NM_001142544.3		c.316C>A	p.Arg106Ser	missense	Exon 3 of 3	NP_001136016.1	Q16619-2
	CTF1	NR_165660.1		n.457C>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.319C>A	p.Arg107Ser	missense	Exon 3 of 3	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.316C>A	p.Arg106Ser	missense	Exon 3 of 3	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147742 Hom.: 0 Cov.: 31

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: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000521 AC: 5 AN: 959156 Hom.: 0 Cov.: 30 AF XY: 0.00000442 AC XY: 2 AN XY: 452416

African (AFR) AF: 0.00 AC: 0 AN: 18754

American (AMR) AF: 0.00 AC: 0 AN: 5126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9130

East Asian (EAS) AF: 0.00 AC: 0 AN: 13330

South Asian (SAS) AF: 0.00 AC: 0 AN: 19312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2288

European-Non Finnish (NFE) AF: 0.00000592 AC: 5 AN: 844018

Other (OTH) AF: 0.00 AC: 0 AN: 34888

GnomAD4 genome AF: 0.00000677 AC: 1 AN: 147742 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71908

African (AFR) AF: 0.00 AC: 0 AN: 41008

American (AMR) AF: 0.00 AC: 0 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66376

Other (OTH) AF: 0.00 AC: 0 AN: 2038

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.34
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.052
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.16	N
REVEL	Benign	0.20
Sift	Benign	0.52	T
Sift4G	Benign	0.17	T
Polyphen		0.30	B
Vest4		0.066
MutPred		0.30		Loss of MoRF binding (P = 0.0399)
MVP		0.70
MPC		0.48
ClinPred		0.17	T
GERP RS		3.7
Varity_R		0.22
gMVP		0.41
Mutation Taster		=82/18	polymorphism

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: rs727502950; hg19: chr16-30913573;