16-30898385-C-G

Variant names:

• chr16-30898385-C-G
• rs11862962
• NM_001330.5:c.26-1030C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001330.5(CTF1):​c.26-1030C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,918 control chromosomes in the GnomAD database, including 5,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5201 hom., cov: 31)
• Consequence: CTF1 NM_001330.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.274
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-30898385-C-G is Benign according to our data. Variant chr16-30898385-C-G is described in ClinVar as Benign. ClinVar VariationId is 1164131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

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.26-1030C>G		intron	N/A	NP_001321.1	Q16619-1
	CTF1	NM_001142544.3		c.26-1033C>G		intron	N/A	NP_001136016.1	Q16619-2
	CTF1	NR_165660.1		n.56-922C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	ENST00000279804.3	TSL:1 MANE Select	c.26-1030C>G		intron	N/A	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.26-1033C>G		intron	N/A	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37248 AN: 151800 Hom.: 5205 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37245 AN: 151918 Hom.: 5201 Cov.: 31 AF XY: 0.251 AC XY: 18630 AN XY: 74220

African (AFR) AF: 0.183 AC: 7605 AN: 41474

American (AMR) AF: 0.202 AC: 3084 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 940 AN: 3456

East Asian (EAS) AF: 0.0860 AC: 444 AN: 5164

South Asian (SAS) AF: 0.680 AC: 3275 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2821 AN: 10542

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18195 AN: 67890

Other (OTH) AF: 0.246 AC: 518 AN: 2104

Alfa AF: 0.162 Hom.: 333

Bravo AF: 0.225

Asia WGS AF: 0.397 AC: 1378 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dilated Cardiomyopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.24
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs11862962; hg19: chr16-30909706;