chr20-57503634-G-A

Variant names:

• chr20-57503634-G-A
• rs6128059
• NM_001386993.1:c.1675-33C>T

Variant summary

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

The NM_001386993.1(CTCFL):​c.1675-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,610,770 control chromosomes in the GnomAD database, including 67,472 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 0.23 (4585 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62887 hom.)
• Consequence: CTCFL NM_001386993.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386993.1. 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.1675-33C>T		intron	N/A	NP_001373922.1
	CTCFL	NM_001269043.2		c.1675-33C>T		intron	N/A	NP_001255972.1
	CTCFL	NM_001269044.3		c.1675-33C>T		intron	N/A	NP_001255973.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.1675-33C>T		intron	N/A	ENSP00000243914.3
	CTCFL	ENST00000423479.7	TSL:1	c.1675-33C>T		intron	N/A	ENSP00000415579.2
	CTCFL	ENST00000608440.5	TSL:1	c.1675-33C>T		intron	N/A	ENSP00000477488.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34626 AN: 151984 Hom.: 4585 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.231

GnomAD2 exomes AF: 0.257 AC: 64096 AN: 249666 AF XY: 0.272

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.210

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.289 AC: 421000 AN: 1458668 Hom.: 62887 Cov.: 32 AF XY: 0.293 AC XY: 212595 AN XY: 725388

African (AFR) AF: 0.104 AC: 3463 AN: 33424

American (AMR) AF: 0.151 AC: 6757 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 6801 AN: 26006

East Asian (EAS) AF: 0.211 AC: 8364 AN: 39624

South Asian (SAS) AF: 0.379 AC: 32643 AN: 86060

European-Finnish (FIN) AF: 0.213 AC: 11313 AN: 53226

Middle Eastern (MID) AF: 0.329 AC: 1882 AN: 5720

European-Non Finnish (NFE) AF: 0.300 AC: 333003 AN: 1109758

Other (OTH) AF: 0.278 AC: 16774 AN: 60238

GnomAD4 genome AF: 0.228 AC: 34619 AN: 152102 Hom.: 4585 Cov.: 32 AF XY: 0.224 AC XY: 16657 AN XY: 74342

African (AFR) AF: 0.113 AC: 4682 AN: 41500

American (AMR) AF: 0.194 AC: 2965 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1080 AN: 5172

South Asian (SAS) AF: 0.354 AC: 1703 AN: 4814

European-Finnish (FIN) AF: 0.213 AC: 2251 AN: 10570

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20219 AN: 67982

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.268 Hom.: 7647

Bravo AF: 0.220

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.80
PhyloP100		-0.40
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: rs6128059; hg19: chr20-56078690; COSMIC: COSV54778836; COSMIC: COSV54778836;