rs73625091

Positions:

• chr20-57524818-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000243914.8(CTCFL):​c.-12+209del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 937,962 control chromosomes in the GnomAD database, including 1,421 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.057 (599 hom., cov: 32)
  • Exomes 𝑓: 0.039 (822 hom.)
• Consequence: CTCFL ENST00000243914.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTCFL	NM_001386993.1	c.-12+209del		intron_variant		ENST00000243914.8	NP_001373922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTCFL	ENST00000243914.8	c.-12+209del		intron_variant		1	NM_001386993.1	ENSP00000243914	P4

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8706 AN: 152078 Hom.: 595 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.0991

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0630

GnomAD4 exome AF: 0.0392 AC: 30774 AN: 785766 Hom.: 822 Cov.: 9 AF XY: 0.0389 AC XY: 14177 AN XY: 364358

Gnomad4 AFR exome AF: 0.00452

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.0566

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.0857

Gnomad4 FIN exome AF: 0.0797

Gnomad4 NFE exome AF: 0.0367

Gnomad4 OTH exome AF: 0.0566

GnomAD4 genome AF: 0.0573 AC: 8719 AN: 152196 Hom.: 599 Cov.: 32 AF XY: 0.0630 AC XY: 4686 AN XY: 74388

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.0984

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.0671

Alfa AF: 0.0175 Hom.: 8

Bravo AF: 0.0623

Asia WGS AF: 0.199 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs73625091; hg19: chr20-56099874;