ENST00000422109.6:n.-44C>T

Variant names:

• chr20-57524911-T-A
• NM_001386993.1:c.-12+117A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000422109.6(CTCFL):​n.-706A>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTCFL ENST00000422109.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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+117A>T		intron	N/A	NP_001373922.1
	CTCFL	NM_001269043.2		c.-12+117A>T		intron	N/A	NP_001255972.1
	CTCFL	NM_001269040.2		c.-12+563A>T		intron	N/A	NP_001255969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.-12+117A>T		intron	N/A	ENSP00000243914.3
	CTCFL	ENST00000423479.7	TSL:1	c.-12+117A>T		intron	N/A	ENSP00000415579.2
	CTCFL	ENST00000371196.6	TSL:1	c.-12+563A>T		intron	N/A	ENSP00000360239.2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 113178 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 53820

African (AFR) AF: 0.00 AC: 0 AN: 2056

American (AMR) AF: 0.00 AC: 0 AN: 126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 728

East Asian (EAS) AF: 0.00 AC: 0 AN: 480

South Asian (SAS) AF: 0.00 AC: 0 AN: 2306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 103600

Other (OTH) AF: 0.00 AC: 0 AN: 3622

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.65
PhyloP100		-0.57
PromoterAI		0.17	Neutral

Splicing

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

Other links and lift over

hg19: chr20-56099967;