Genetic Variant NM_006565.4:c.-9-11C>T (chr16-67610813-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006565.4(CTCF):c.-9-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,447,888 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 Benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

CTCF
NM_006565.4 intron

Scores

Splicing: ADA: 0.0002395

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.720

Publications

0 publications found

Variant links:

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

CTCF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 16-67610813-C-T is Benign according to our data. Variant chr16-67610813-C-T is described in ClinVar as Benign. ClinVar VariationId is 1242208.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000545 (83/152206) while in subpopulation AFR AF = 0.00183 (76/41524). AF 95% confidence interval is 0.0015. There are 1 homozygotes in GnomAd4. There are 36 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 83 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTCF	NM_006565.4	MANE Select	c.-9-11C>T	intron	N/A	NP_006556.1	P49711-1
CTCF	NM_001438968.1		c.-9-11C>T	intron	N/A	NP_001425897.1
CTCF	NM_001363916.2		c.-9-11C>T	intron	N/A	NP_001350845.1	A0A2R8YFL0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTCF	ENST00000264010.10	TSL:1 MANE Select	c.-9-11C>T	intron	N/A	ENSP00000264010.4	P49711-1
CTCF	ENST00000401394.6	TSL:1	c.-32-5932C>T	intron	N/A	ENSP00000384707.1	P49711-2
CTCF	ENST00000645699.1		c.-20C>T	5_prime_UTR	Exon 1 of 10	ENSP00000495348.1	P49711-1

Frequencies

GnomAD3 genomes

AF:

0.000546

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000205

AC:

AN:

170710

AF XY:

0.0000887

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1295682

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

627914

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

29462

American (AMR)

AF:

0.00

AC:

AN:

26100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18506

East Asian (EAS)

AF:

0.00

AC:

AN:

37696

South Asian (SAS)

AF:

0.0000968

AC:

AN:

51656

European-Finnish (FIN)

AF:

0.0000212

AC:

AN:

47248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5072

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1026818

Other (OTH)

AF:

0.0000565

AC:

AN:

53124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000545

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

41524

American (AMR)

AF:

0.000196

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000277

Hom.:

Bravo

AF:

0.000631

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.72

PromoterAI

-0.0040

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.086

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over