rs6128059

chr20-57503634-G-Achr20-57503634-G-T

Variant summary

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

The NM_001386993.1(CTCFL):c.1675-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,610,770 control chromosomes in the GnomAD database, including 67,472 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 0.23 (4585 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62887 hom.)
• Consequence: CTCFL NM_001386993.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTCFL	NM_001386993.1	c.1675-33C>T		intron_variant		ENST00000243914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTCFL	ENST00000243914.8	c.1675-33C>T		intron_variant		1	NM_001386993.1	P4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34626 AN: 151984 Hom.: 4585 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.231

GnomAD3 exomes AF: 0.257 AC: 64096 AN: 249666 Hom.: 9087 AF XY: 0.272 AC XY: 36676 AN XY: 134980

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.210

Gnomad SAS exome AF: 0.377

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.289 AC: 421000 AN: 1458668 Hom.: 62887 Cov.: 32 AF XY: 0.293 AC XY: 212595 AN XY: 725388

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.228 AC: 34619 AN: 152102 Hom.: 4585 Cov.: 32 AF XY: 0.224 AC XY: 16657 AN XY: 74342

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.229

Alfa AF: 0.276 Hom.: 6099

Bravo AF: 0.220

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.80

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: rs6128059; hg19: chr20-56078690; COSMIC: COSV54778836; COSMIC: COSV54778836;