chr16-67610546-G-A

Position:

• chr16-67610546-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006565.4(CTCF):​c.-9-278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 160,470 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (222 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (4 hom.)
• Consequence: CTCF NM_006565.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.198

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-67610546-G-A is Benign according to our data. Variant chr16-67610546-G-A is described in ClinVar as [Benign]. Clinvar id is 1235877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTCF	NM_006565.4	c.-9-278G>A		intron_variant		ENST00000264010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTCF	ENST00000264010.10	c.-9-278G>A		intron_variant		1	NM_006565.4	P4

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4227 AN: 151526 Hom.: 215 Cov.: 31

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000398

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.00567 AC: 50 AN: 8826 Hom.: 4 Cov.: 0 AF XY: 0.00479 AC XY: 21 AN XY: 4382

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.00671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00331

GnomAD4 genome AF: 0.0281 AC: 4264 AN: 151644 Hom.: 222 Cov.: 31 AF XY: 0.0270 AC XY: 2003 AN XY: 74078

Gnomad4 AFR AF: 0.0975

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000626

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000398

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0217 Hom.: 12

Bravo AF: 0.0312

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.89

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: rs111735986; hg19: chr16-67644449;