16-30902524-C-G

Variant names:

• chr16-30902524-C-G
• rs397516652
• NM_001330.5:c.591C>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001330.5(CTF1):​c.591C>G​(p.Pro197Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,496,536 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P197P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: CTF1 NM_001330.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.188
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 16-30902524-C-G is Benign according to our data. Variant chr16-30902524-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.188 with no splicing effect.
• BS2: High AC in GnomAd4 at 232 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	NM_001330.5	MANE Select	c.591C>G	p.Pro197Pro	synonymous	Exon 3 of 3	NP_001321.1
	CTF1	NM_001142544.3		c.588C>G	p.Pro196Pro	synonymous	Exon 3 of 3	NP_001136016.1
	CTF1	NR_165660.1		n.729C>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.591C>G	p.Pro197Pro	synonymous	Exon 3 of 3	ENSP00000279804.2
	CTF1	ENST00000395019.3	TSL:1	c.588C>G	p.Pro196Pro	synonymous	Exon 3 of 3	ENSP00000378465.3

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 232 AN: 152046 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00202

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00208 AC: 214 AN: 103072 AF XY: 0.00204

Gnomad AFR exome AF: 0.000766

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.00130

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00268

Gnomad OTH exome AF: 0.00234

GnomAD4 exome AF: 0.00213 AC: 2866 AN: 1344380 Hom.: 3 Cov.: 30 AF XY: 0.00212 AC XY: 1402 AN XY: 662670

African (AFR) AF: 0.000432 AC: 12 AN: 27782

American (AMR) AF: 0.00436 AC: 143 AN: 32784

Ashkenazi Jewish (ASJ) AF: 0.00105 AC: 25 AN: 23870

East Asian (EAS) AF: 0.00 AC: 0 AN: 31206

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76508

European-Finnish (FIN) AF: 0.000242 AC: 8 AN: 33070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3940

European-Non Finnish (NFE) AF: 0.00242 AC: 2569 AN: 1059550

Other (OTH) AF: 0.00194 AC: 108 AN: 55670

GnomAD4 genome AF: 0.00152 AC: 232 AN: 152156 Hom.: 0 Cov.: 31 AF XY: 0.00153 AC XY: 114 AN XY: 74386

African (AFR) AF: 0.000674 AC: 28 AN: 41544

American (AMR) AF: 0.00353 AC: 54 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00202 AC: 137 AN: 67952

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.000986 Hom.: 1

Bravo AF: 0.00182

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Cardiomyopathy (1)
-	-	1	Dilated Cardiomyopathy, Dominant (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.6
DANN	Benign	0.75
PhyloP100		-0.19
Mutation Taster		=100/0	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: rs397516652; hg19: chr16-30913845;