rs11699220

Variant names:

• chr20-57524249-G-A
• rs11699220
• ENST00000608440.5:c.-44C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-57524249-G-A
• chr20-57524249-G-C
• chr20-57524249-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001269044.3(CTCFL):​c.-44C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,574,958 control chromosomes in the GnomAD database, including 164,639 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 0.37 (11792 hom., cov: 30)
  • Exomes 𝑓: 0.46 (152847 hom.)
• Consequence: CTCFL NM_001269044.3 5_prime_UTR
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001269044.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	NM_001386993.1	MANE Select	c.-11-33C>T		intron	N/A	NP_001373922.1	Q8NI51-1
	CTCFL	NM_001269044.3		c.-44C>T		5_prime_UTR	Exon 1 of 10	NP_001255973.1	Q8NI51-3
	CTCFL	NM_001269041.2		c.-44C>T		5_prime_UTR	Exon 1 of 10	NP_001255970.1	Q8NI51-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000608440.5	TSL:1	c.-44C>T		5_prime_UTR	Exon 1 of 10	ENSP00000477488.1	Q8NI51-3
	CTCFL	ENST00000608263.5	TSL:1	c.-44C>T		5_prime_UTR	Exon 1 of 10	ENSP00000476783.1	Q8NI51-1
	CTCFL	ENST00000432255.6	TSL:1	c.-44C>T		5_prime_UTR	Exon 1 of 6	ENSP00000409344.2	Q8NI51-4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56048 AN: 151608 Hom.: 11803 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.426 AC: 91543 AN: 214728 AF XY: 0.439

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.459 AC: 653622 AN: 1423230 Hom.: 152847 Cov.: 48 AF XY: 0.461 AC XY: 325273 AN XY: 704830

African (AFR) AF: 0.145 AC: 4746 AN: 32688

American (AMR) AF: 0.336 AC: 14129 AN: 42112

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 11762 AN: 23712

East Asian (EAS) AF: 0.364 AC: 14388 AN: 39570

South Asian (SAS) AF: 0.485 AC: 38435 AN: 79216

European-Finnish (FIN) AF: 0.441 AC: 19637 AN: 44538

Middle Eastern (MID) AF: 0.522 AC: 2903 AN: 5564

European-Non Finnish (NFE) AF: 0.475 AC: 520476 AN: 1096782

Other (OTH) AF: 0.460 AC: 27146 AN: 59048

GnomAD4 genome AF: 0.369 AC: 56029 AN: 151728 Hom.: 11792 Cov.: 30 AF XY: 0.369 AC XY: 27378 AN XY: 74136

African (AFR) AF: 0.157 AC: 6486 AN: 41400

American (AMR) AF: 0.373 AC: 5692 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3464

East Asian (EAS) AF: 0.386 AC: 1985 AN: 5136

South Asian (SAS) AF: 0.471 AC: 2262 AN: 4798

European-Finnish (FIN) AF: 0.431 AC: 4505 AN: 10460

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 31986 AN: 67904

Other (OTH) AF: 0.409 AC: 860 AN: 2102

Alfa AF: 0.412 Hom.: 6147

Bravo AF: 0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.62
PhyloP100		0.85
PromoterAI		-0.0032	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV105035079;