NM_001386993.1:c.1675-1392A>G

Variant names:

• chr20-57504993-T-C
• rs11700100
• NM_001386993.1:c.1675-1392A>G

Variant summary

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

The NM_001386993.1(CTCFL):​c.1675-1392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,672 control chromosomes in the GnomAD database, including 7,104 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 0.26 (7104 hom., cov: 32)
• Consequence: CTCFL NM_001386993.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTCFL	NM_001386993.1	c.1675-1392A>G		intron_variant	Intron 9 of 10	ENST00000243914.8	NP_001373922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTCFL	ENST00000243914.8	c.1675-1392A>G		intron_variant	Intron 9 of 10	1	NM_001386993.1	ENSP00000243914.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38841 AN: 151554 Hom.: 7100 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38856 AN: 151672 Hom.: 7104 Cov.: 32 AF XY: 0.259 AC XY: 19195 AN XY: 74102

African (AFR) AF: 0.0595 AC: 2468 AN: 41500

American (AMR) AF: 0.298 AC: 4533 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3468

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5176

South Asian (SAS) AF: 0.308 AC: 1483 AN: 4818

European-Finnish (FIN) AF: 0.403 AC: 4222 AN: 10476

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24031 AN: 67700

Other (OTH) AF: 0.258 AC: 544 AN: 2106

Alfa AF: 0.309 Hom.: 13084

Bravo AF: 0.238

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.77
PhyloP100		0.31
Mutation Taster		=100/0	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: rs11700100; hg19: chr20-56080049;