NM_001386993.1:c.544-66A>C

Variant names:

• chr20-57523344-T-G
• rs66593447
• NM_001386993.1:c.544-66A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001386993.1(CTCFL):​c.544-66A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,434,458 control chromosomes in the GnomAD database, including 1,465 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 0.029 (110 hom., cov: 33)
  • Exomes 𝑓: 0.042 (1355 hom.)
• Consequence: CTCFL NM_001386993.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 2 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=-0.79).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0289 (4398/152322) while in subpopulation NFE AF = 0.0483 (3285/68036). AF 95% confidence interval is 0.0469. There are 110 homozygotes in GnomAd4. There are 1934 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 110 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTCFL	NM_001386993.1	c.544-66A>C		intron_variant	Intron 2 of 10	ENST00000243914.8	NP_001373922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTCFL	ENST00000243914.8	c.544-66A>C		intron_variant	Intron 2 of 10	1	NM_001386993.1	ENSP00000243914.3

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4400 AN: 152204 Hom.: 110 Cov.: 33

Gnomad AFR AF: 0.00787

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0483

Gnomad OTH AF: 0.0291

GnomAD4 exome AF: 0.0416 AC: 53339 AN: 1282136 Hom.: 1355 AF XY: 0.0408 AC XY: 26132 AN XY: 640648

African (AFR) AF: 0.00731 AC: 210 AN: 28740

American (AMR) AF: 0.0159 AC: 566 AN: 35508

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 738 AN: 22756

East Asian (EAS) AF: 0.000104 AC: 4 AN: 38592

South Asian (SAS) AF: 0.0110 AC: 826 AN: 74834

European-Finnish (FIN) AF: 0.0217 AC: 1033 AN: 47502

Middle Eastern (MID) AF: 0.0238 AC: 91 AN: 3826

European-Non Finnish (NFE) AF: 0.0490 AC: 47900 AN: 976562

Other (OTH) AF: 0.0366 AC: 1971 AN: 53816

GnomAD4 genome AF: 0.0289 AC: 4398 AN: 152322 Hom.: 110 Cov.: 33 AF XY: 0.0260 AC XY: 1934 AN XY: 74478

African (AFR) AF: 0.00785 AC: 326 AN: 41554

American (AMR) AF: 0.0202 AC: 309 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4830

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0483 AC: 3285 AN: 68036

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0178 Hom.: 8

Bravo AF: 0.0285

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.71
DANN	Benign	0.67
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs66593447; hg19: chr20-56098400;