20-57524249-G-C

Variant names:

• chr20-57524249-G-C
• rs11699220
• ENST00000422109.6:n.-44C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000422109.6(CTCFL):​n.-44C>G 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 0.000175 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 ENST00000422109.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852
• Publications: 8 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.-11-33C>G		intron	N/A	NP_001373922.1
	CTCFL	NR_072975.3		n.449C>G		non_coding_transcript_exon	Exon 1 of 11
	CTCFL	NR_170377.1		n.449C>G		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000422109.6	TSL:1	n.-44C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000413713.2
	CTCFL	ENST00000426658.6	TSL:1	n.-44C>G		non_coding_transcript_exon	Exon 1 of 11	ENSP00000403369.2
	CTCFL	ENST00000607923.5	TSL:1	n.619C>G		non_coding_transcript_exon	Exon 1 of 5

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

GnomAD2 exomes AF: 0.000214 AC: 46 AN: 214728 AF XY: 0.000233

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 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

African (AFR) AF: 0.000153 AC: 5 AN: 32702

American (AMR) AF: 0.00 AC: 0 AN: 42138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23722

East Asian (EAS) AF: 0.000581 AC: 23 AN: 39570

South Asian (SAS) AF: 0.000114 AC: 9 AN: 79250

European-Finnish (FIN) AF: 0.000135 AC: 6 AN: 44562

Middle Eastern (MID) AF: 0.000539 AC: 3 AN: 5564

European-Non Finnish (NFE) AF: 0.000170 AC: 187 AN: 1096854

Other (OTH) AF: 0.000305 AC: 18 AN: 59054

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

African (AFR) AF: 0.000121 AC: 5 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000236 AC: 16 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000110 Hom.: 6147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		0.85
PromoterAI		0.032	Neutral

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

Other links and lift over

dbSNP: rs11699220; hg19: chr20-56099305;