rs11699220

chr20-57524249-G-Achr20-57524249-G-Cchr20-57524249-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000608440.5(CTCFL):c.-44C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,574,958 control chromosomes in the GnomAD database, including 164,639 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11792 hom., cov: 30)
  • Exomes 𝑓: 0.46 (152847 hom.)
• Consequence: CTCFL ENST00000608440.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTCFL	NM_001386993.1	c.-11-33C>T		intron_variant		ENST00000243914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTCFL	ENST00000243914.8	c.-11-33C>T		intron_variant		1	NM_001386993.1	P4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56048 AN: 151608 Hom.: 11803 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.414

GnomAD3 exomes AF: 0.426 AC: 91543 AN: 214728 Hom.: 20482 AF XY: 0.439 AC XY: 50879 AN XY: 115892

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.393

Gnomad SAS exome AF: 0.492

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.459 AC: 653622 AN: 1423230 Hom.: 152847 Cov.: 48 AF XY: 0.461 AC XY: 325273 AN XY: 704830

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.369 AC: 56029 AN: 151728 Hom.: 11792 Cov.: 30 AF XY: 0.369 AC XY: 27378 AN XY: 74136

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.409

Alfa AF: 0.408 Hom.: 3829

Bravo AF: 0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.1
Dann	Benign	0.62

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: rs11699220; hg19: chr20-56099305; COSMIC: COSV105035079;