rs73625093

Positions:

• chr20-57508717-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001386993.1(CTCFL):​c.1563A>G​(p.Lys521=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,614,176 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (8 hom.)
• Consequence: CTCFL NM_001386993.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-57508717-T-C is Benign according to our data. Variant chr20-57508717-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2652425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTCFL	NM_001386993.1	c.1563A>G	p.Lys521=	synonymous_variant	9/11	ENST00000243914.8	NP_001373922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTCFL	ENST00000243914.8	c.1563A>G	p.Lys521=	synonymous_variant	9/11	1	NM_001386993.1	ENSP00000243914	P4

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00165 AC: 415 AN: 251482 Hom.: 1 AF XY: 0.00175 AC XY: 238 AN XY: 135916

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00186

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00242

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00179 AC: 2619 AN: 1461864 Hom.: 8 Cov.: 31 AF XY: 0.00188 AC XY: 1369 AN XY: 727232

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00226

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00193

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74486

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00212 Hom.: 0

Bravo AF: 0.00157

EpiCase AF: 0.00327

EpiControl AF: 0.00391

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

Nov 01, 2022

CTCFL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.41
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: rs73625093; hg19: chr20-56083773;