dbSNP rs149766428: CTCF:p.Ala629Ala (chr16-67636739-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006565.4(CTCF):c.1887C>T(p.Ala629Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,609,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

CTCF
NM_006565.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.02

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-67636739-C-T is Benign according to our data. Variant chr16-67636739-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000421 (64/151870) while in subpopulation NFE AF = 0.000544 (37/67988). AF 95% confidence interval is 0.000405. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 64 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	HGVSp	Effect	Exon Rank	Protein	UniProt
CTCF	NM_006565.4	MANE Select	c.1887C>T	p.Ala629Ala	synonymous	Exon 11 of 12	NP_006556.1	P49711-1
CTCF	NM_001438968.1		c.1887C>T	p.Ala629Ala	synonymous	Exon 11 of 12	NP_001425897.1
CTCF	NM_001363916.2		c.1887C>T	p.Ala629Ala	synonymous	Exon 11 of 12	NP_001350845.1	A0A2R8YFL0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTCF	ENST00000264010.10	TSL:1 MANE Select	c.1887C>T	p.Ala629Ala	synonymous	Exon 11 of 12	ENSP00000264010.4	P49711-1
CTCF	ENST00000401394.6	TSL:1	c.903C>T	p.Ala301Ala	synonymous	Exon 9 of 10	ENSP00000384707.1	P49711-2
CTCF	ENST00000642819.1		c.1887C>T	p.Ala629Ala	synonymous	Exon 10 of 11	ENSP00000494408.1	P49711-1

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000962

GnomAD2 exomes

AF:

0.000407

AC:

101

AN:

247958

AF XY:

0.000366

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.000271

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000628

Gnomad OTH exome

AF:

0.000837

GnomAD4 exome

AF:

0.000653

AC:

952

AN:

1457460

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

468

AN XY:

724794

show subpopulations

African (AFR)

AF:

0.000480

AC:

AN:

33328

American (AMR)

AF:

0.000226

AC:

AN:

44156

Ashkenazi Jewish (ASJ)

AF:

0.000690

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39446

South Asian (SAS)

AF:

0.0000939

AC:

AN:

85170

European-Finnish (FIN)

AF:

0.000244

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000769

AC:

853

AN:

1109898

Other (OTH)

AF:

0.000548

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

137

182

228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<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:

0.000421

AC:

AN:

151870

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.000387

AC:

AN:

41314

American (AMR)

AF:

0.000328

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

67988

Other (OTH)

AF:

0.000962

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000523

Hom.:

Bravo

AF:

0.000461

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.58

(source)

DANN

Benign

0.69

PhyloP100

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

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