20-57503443-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001386993.1(CTCFL):c.1833C>T(p.Asn611=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,122 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: CTCFL NM_001386993.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.59

Genes affected

CTCFL (HGNC:16234): (CCCTC-binding factor like) CCCTC-binding factor (CTCF), an 11-zinc-finger factor involved in gene regulation, utilizes different zinc fingers to bind varying DNA target sites. CTCF forms methylation-sensitive insulators that regulate X-chromosome inactivation. This gene is a paralog of CTCF and appears to be expressed primarily in the cytoplasm of spermatocytes, unlike CTCF which is expressed primarily in the nucleus of somatic cells. CTCF and the protein encoded by this gene are normally expressed in a mutually exclusive pattern that correlates with resetting of methylation marks during male germ cell differentiation. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-57503443-G-A is Benign according to our data. Variant chr20-57503443-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652424.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.59 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTCFL	NM_001386993.1	c.1833C>T	p.Asn611=	synonymous_variant	10/11	ENST00000243914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTCFL	ENST00000243914.8	c.1833C>T	p.Asn611=	synonymous_variant	10/11	1	NM_001386993.1	P4

Frequencies

GnomAD3 genomes AF: 0.00128 AC: 195 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00156 AC: 393 AN: 251382 Hom.: 0 AF XY: 0.00171 AC XY: 232 AN XY: 135860

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00219

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00173 AC: 2525 AN: 1461798 Hom.: 6 Cov.: 31 AF XY: 0.00182 AC XY: 1323 AN XY: 727204

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.00188

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00128 AC: 195 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74484

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00218 Hom.: 0

Bravo AF: 0.00145

EpiCase AF: 0.00316

EpiControl AF: 0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

CTCFL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.90
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs138934649; hg19: chr20-56078499; COSMIC: COSV54780072; COSMIC: COSV54780072;