rs73625091

Variant names:

• chr20-57524818-CA-C
• rs73625091
• ENST00000422109.6:n.-614delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000422109.6(CTCFL):​n.-614delT variant causes a non coding transcript exon 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 ENST00000422109.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422109.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	NM_001386993.1	MANE Select	c.-12+209delT		intron	N/A	NP_001373922.1
	CTCFL	NM_001269043.2		c.-12+209delT		intron	N/A	NP_001255972.1
	CTCFL	NM_001269040.2		c.-11-603delT		intron	N/A	NP_001255969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000422109.6	TSL:1	n.-614delT		non_coding_transcript_exon	Exon 1 of 8	ENSP00000413713.2
	CTCFL	ENST00000426658.6	TSL:1	n.-614delT		non_coding_transcript_exon	Exon 1 of 11	ENSP00000403369.2
	CTCFL	ENST00000607923.5	TSL:1	n.49delT		non_coding_transcript_exon	Exon 1 of 5

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

African (AFR) AF: 0.00452 AC: 67 AN: 14812

American (AMR) AF: 0.190 AC: 190 AN: 1002

Ashkenazi Jewish (ASJ) AF: 0.0566 AC: 274 AN: 4840

East Asian (EAS) AF: 0.283 AC: 967 AN: 3418

South Asian (SAS) AF: 0.0857 AC: 1334 AN: 15574

European-Finnish (FIN) AF: 0.0797 AC: 22 AN: 276

Middle Eastern (MID) AF: 0.0640 AC: 99 AN: 1546

European-Non Finnish (NFE) AF: 0.0367 AC: 26364 AN: 718568

Other (OTH) AF: 0.0566 AC: 1457 AN: 25730

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

African (AFR) AF: 0.0103 AC: 430 AN: 41570

American (AMR) AF: 0.160 AC: 2454 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1482 AN: 5124

South Asian (SAS) AF: 0.0984 AC: 474 AN: 4818

European-Finnish (FIN) AF: 0.0754 AC: 800 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2717 AN: 67984

Other (OTH) AF: 0.0671 AC: 142 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73625091; hg19: chr20-56099874;