rs6128059

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-57503634-G-A
• chr20-57503634-G-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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTCFL	NM_001386993.1	c.1675-33C>T		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.1675-33C>T		intron_variant	Intron 9 of 10	1	NM_001386993.1	ENSP00000243914.3

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

Gnomad4 AFR exome AF: 0.104 AC: 3463 AN: 33424

Gnomad4 AMR exome AF: 0.151 AC: 6757 AN: 44612

Gnomad4 ASJ exome AF: 0.262 AC: 6801 AN: 26006

Gnomad4 EAS exome AF: 0.211 AC: 8364 AN: 39624

Gnomad4 SAS exome AF: 0.379 AC: 32643 AN: 86060

Gnomad4 FIN exome AF: 0.213 AC: 11313 AN: 53226

Gnomad4 NFE exome AF: 0.300 AC: 333003 AN: 1109758

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.113 AC: 0.112819 AN: 0.112819

Gnomad4 AMR AF: 0.194 AC: 0.19407 AN: 0.19407

Gnomad4 ASJ AF: 0.262 AC: 0.261671 AN: 0.261671

Gnomad4 EAS AF: 0.209 AC: 0.208817 AN: 0.208817

Gnomad4 SAS AF: 0.354 AC: 0.35376 AN: 0.35376

Gnomad4 FIN AF: 0.213 AC: 0.212961 AN: 0.212961

Gnomad4 NFE AF: 0.297 AC: 0.297417 AN: 0.297417

Gnomad4 OTH AF: 0.229 AC: 0.22891 AN: 0.22891

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.80
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

Publications

LitVar

Other links and lift over

dbSNP: rs6128059; hg19: chr20-56078690; COSMIC: COSV54778836; COSMIC: COSV54778836;