16-67565853-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006565.4(CTCF):c.-127+3129G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 152,312 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0033 (1 hom., cov: 30)
• Consequence: CTCF NM_006565.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.338

Genes affected

CTCF (HGNC:13723): (CCCTC-binding factor) This gene is a member of the BORIS + CTCF gene family and encodes a transcriptional regulator protein with 11 highly conserved zinc finger (ZF) domains. This nuclear protein is able to use different combinations of the ZF domains to bind different DNA target sequences and proteins. Depending upon the context of the site, the protein can bind a histone acetyltransferase (HAT)-containing complex and function as a transcriptional activator or bind a histone deacetylase (HDAC)-containing complex and function as a transcriptional repressor. If the protein is bound to a transcriptional insulator element, it can block communication between enhancers and upstream promoters, thereby regulating imprinted expression. Mutations in this gene have been associated with invasive breast cancers, prostate cancers, and Wilms' tumors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 16-67565853-G-T is Benign according to our data. Variant chr16-67565853-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00328 (499/152312) while in subpopulation AMR AF= 0.00562 (86/15290). AF 95% confidence interval is 0.00466. There are 1 homozygotes in gnomad4. There are 254 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 500 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTCF	NM_006565.4	c.-127+3129G>T		intron_variant		ENST00000264010.10
CTCF	NM_001191022.2	c.-150+3129G>T		intron_variant
CTCF	XM_005255775.4	c.-127+3129G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTCF	ENST00000264010.10	c.-127+3129G>T		intron_variant		1	NM_006565.4	P4

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 500 AN: 152194 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.00328 AC: 499 AN: 152312 Hom.: 1 Cov.: 30 AF XY: 0.00341 AC XY: 254 AN XY: 74478

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00415

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00349 Hom.: 0

Bravo AF: 0.00355

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CTCF: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	8.1
Dann	Benign	0.73

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: rs111278790; hg19: chr16-67599756;