rs73625090

chr20-57524980-A-T

Variant summary

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

The NM_001386993.1(CTCFL):c.-12+48T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 147,736 control chromosomes in the GnomAD database, including 118 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 0.037 (116 hom., cov: 29)
  • Exomes 𝑓: 0.024 (2 hom.)
• Consequence: CTCFL NM_001386993.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTCFL	NM_001386993.1	c.-12+48T>A		intron_variant		ENST00000243914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTCFL	ENST00000243914.8	c.-12+48T>A		intron_variant		1	NM_001386993.1	P4

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5434 AN: 145522 Hom.: 116 Cov.: 29

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.0709

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0316

Gnomad EAS AF: 0.00458

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0484

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0391

GnomAD4 exome AF: 0.0243 AC: 51 AN: 2100 Hom.: 2 Cov.: 0 AF XY: 0.0223 AC XY: 24 AN XY: 1076

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0435

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0214

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0374 AC: 5441 AN: 145636 Hom.: 116 Cov.: 29 AF XY: 0.0362 AC XY: 2575 AN XY: 71048

Gnomad4 AFR AF: 0.0616

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0316

Gnomad4 EAS AF: 0.00459

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0296

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0302 Hom.: 10

Bravo AF: 0.0388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.054
Dann	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73625090; hg19: chr20-56100036;