chr16-67637901-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006565.4(CTCF):c.*29T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,552,148 control chromosomes in the GnomAD database, including 10,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2698 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7402 hom. )

Consequence

CTCF
NM_006565.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.500

Publications

36 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 16-67637901-T-G is Benign according to our data. Variant chr16-67637901-T-G is described in ClinVar as Benign. ClinVar VariationId is 1244031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CTCF	NM_006565.4	MANE Select	c.*29T>G	3_prime_UTR	Exon 12 of 12	NP_006556.1
CTCF	NM_001438968.1		c.*29T>G	3_prime_UTR	Exon 12 of 12	NP_001425897.1
CTCF	NM_001363916.2		c.*29T>G	3_prime_UTR	Exon 12 of 12	NP_001350845.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CTCF	ENST00000264010.10	TSL:1 MANE Select	c.*29T>G	3_prime_UTR	Exon 12 of 12	ENSP00000264010.4
CTCF	ENST00000401394.6	TSL:1	c.*29T>G	3_prime_UTR	Exon 10 of 10	ENSP00000384707.1
CTCF	ENST00000642420.1		n.902T>G	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22805

AN:

152094

Hom.:

2672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0829

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0841

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.103

AC:

23287

AN:

225612

AF XY:

0.100

show subpopulations

Gnomad AFR exome

AF:

0.327

Gnomad AMR exome

AF:

0.0551

Gnomad ASJ exome

AF:

0.0539

Gnomad EAS exome

AF:

0.0128

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.0897

Gnomad OTH exome

AF:

0.0884

GnomAD4 exome

AF:

0.0923

AC:

129163

AN:

1399936

Hom.:

7402

Cov.:

AF XY:

0.0925

AC XY:

64067

AN XY:

692944

show subpopulations

African (AFR)

AF:

0.348

AC:

11020

AN:

31706

American (AMR)

AF:

0.0559

AC:

2021

AN:

36144

Ashkenazi Jewish (ASJ)

AF:

0.0504

AC:

1196

AN:

23744

East Asian (EAS)

AF:

0.0121

AC:

469

AN:

38902

South Asian (SAS)

AF:

0.119

AC:

9445

AN:

79370

European-Finnish (FIN)

AF:

0.122

AC:

6283

AN:

51554

Middle Eastern (MID)

AF:

0.0765

AC:

296

AN:

3870

European-Non Finnish (NFE)

AF:

0.0863

AC:

93007

AN:

1077486

Other (OTH)

AF:

0.0949

AC:

5426

AN:

57160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5665

11329

16994

22658

28323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3552

7104

10656

14208

17760

<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:

0.150

AC:

22883

AN:

152212

Hom.:

2698

Cov.:

AF XY:

0.149

AC XY:

11077

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.324

AC:

13439

AN:

41506

American (AMR)

AF:

0.0826

AC:

1263

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3470

East Asian (EAS)

AF:

0.0133

AC:

AN:

5186

South Asian (SAS)

AF:

0.111

AC:

537

AN:

4830

European-Finnish (FIN)

AF:

0.126

AC:

1342

AN:

10610

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0841

AC:

5721

AN:

68012

Other (OTH)

AF:

0.125

AC:

263

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

924

1849

2773

3698

4622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.0877

Hom.:

1813

Bravo

AF:

0.153

Asia WGS

AF:

0.105

AC:

368

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.9

(source)

DANN

Benign

0.64

PhyloP100

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over