20-57524249-G-C

Position:

• chr20-57524249-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000608440.5(CTCFL):​c.-44C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,575,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00018 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 23 AN: 151660 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000214 AC: 46 AN: 214728 Hom.: 0 AF XY: 0.000233 AC XY: 27 AN XY: 115892

Gnomad AFR exome AF: 0.0000674

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000444

Gnomad SAS exome AF: 0.0000859

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.000377

GnomAD4 exome AF: 0.000176 AC: 251 AN: 1423416 Hom.: 0 Cov.: 48 AF XY: 0.000173 AC XY: 122 AN XY: 704924

Gnomad4 AFR exome AF: 0.000153

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000581

Gnomad4 SAS exome AF: 0.000114

Gnomad4 FIN exome AF: 0.000135

Gnomad4 NFE exome AF: 0.000170

Gnomad4 OTH exome AF: 0.000305

GnomAD4 genome AF: 0.000158 AC: 24 AN: 151780 Hom.: 0 Cov.: 30 AF XY: 0.000148 AC XY: 11 AN XY: 74170

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000180 Hom.: 3829

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.57

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;