chr16-67593732-G-T

Variant names:

• chr16-67593732-G-T
• rs17686899
• NM_006565.4:c.-9-17092G>T

Variant summary

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

The NM_006565.4(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 NM_006565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 13 publications found

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]

CTCF Gene-Disease associations (from GenCC):

• intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCF	NM_006565.4	MANE Select	c.-9-17092G>T		intron	N/A	NP_006556.1
	CTCF	NM_001438968.1		c.-9-17092G>T		intron	N/A	NP_001425897.1
	CTCF	NM_001363916.2		c.-9-17092G>T		intron	N/A	NP_001350845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCF	ENST00000264010.10	TSL:1 MANE Select	c.-9-17092G>T		intron	N/A	ENSP00000264010.4
	CTCF	ENST00000401394.6	TSL:1	c.-33+22468G>T		intron	N/A	ENSP00000384707.1
	CTCF	ENST00000642819.1		c.-9-17092G>T		intron	N/A	ENSP00000494408.1

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

African (AFR) AF: 0.0323 AC: 1343 AN: 41536

American (AMR) AF: 0.0304 AC: 464 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3468

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5190

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4824

European-Finnish (FIN) AF: 0.0239 AC: 253 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3737 AN: 68018

Other (OTH) AF: 0.0442 AC: 93 AN: 2104

Alfa AF: 0.0481 Hom.: 254

Bravo AF: 0.0418

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.57
PhyloP100		-0.16
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: rs17686899; hg19: chr16-67627635;