chr16-67593732-G-T

Position:

• chr16-67593732-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264010.10(CTCF):​c.-9-17092G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 152,220 control chromosomes in the GnomAD database, including 139 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 0.042 (139 hom., cov: 31)
• Consequence: CTCF ENST00000264010.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTCF	NM_006565.4	c.-9-17092G>T		intron_variant		ENST00000264010.10	NP_006556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTCF	ENST00000264010.10	c.-9-17092G>T		intron_variant		1	NM_006565.4	ENSP00000264010.4

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6345 AN: 152102 Hom.: 139 Cov.: 31

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.0672

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0427

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

GnomAD4 genome AF: 0.0417 AC: 6349 AN: 152220 Hom.: 139 Cov.: 31 AF XY: 0.0398 AC XY: 2961 AN XY: 74436

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0442

Alfa AF: 0.0486 Hom.: 201

Bravo AF: 0.0418

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.57

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: rs17686899; hg19: chr16-67627635;