rs7191281

chr16-67621230-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006565.4(CTCF):c.1208-212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 469,084 control chromosomes in the GnomAD database, including 6,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3292 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2872 hom.)
• Consequence: CTCF NM_006565.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.03

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=-1.22).
• BP6: Variant 16-67621230-T-C is Benign according to our data. Variant chr16-67621230-T-C is described in ClinVar as [Benign]. Clinvar id is 1263720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTCF	NM_006565.4	c.1208-212T>C		intron_variant		ENST00000264010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTCF	ENST00000264010.10	c.1208-212T>C		intron_variant		1	NM_006565.4	P4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27304 AN: 151726 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.122 AC: 38614 AN: 317240 Hom.: 2872 Cov.: 4 AF XY: 0.119 AC XY: 19571 AN XY: 163904

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.0885

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.0119

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.180 AC: 27383 AN: 151844 Hom.: 3292 Cov.: 32 AF XY: 0.177 AC XY: 13169 AN XY: 74212

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.164

Alfa AF: 0.134 Hom.: 1992

Bravo AF: 0.181

Asia WGS AF: 0.112 AC: 392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
Cadd	Benign	0.16
Dann	Benign	0.58

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: rs7191281; hg19: chr16-67655133;