chr16-67610963-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_006565.4(CTCF):ā€‹c.131A>Gā€‹(p.Gln44Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,593,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q44K) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000048 ( 0 hom. )

Consequence

CTCF
NM_006565.4 missense

Scores

1
3
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.48
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CTCF. . Gene score misZ 4.4399 (greater than the threshold 3.09). Trascript score misZ 4.8366 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.034507275).
BP6
Variant 16-67610963-A-G is Benign according to our data. Variant chr16-67610963-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1701292.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTCFNM_006565.4 linkuse as main transcriptc.131A>G p.Gln44Arg missense_variant 3/12 ENST00000264010.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTCFENST00000264010.10 linkuse as main transcriptc.131A>G p.Gln44Arg missense_variant 3/121 NM_006565.4 P4P49711-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00144
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:
0.00
GnomAD3 exomes
AF:
0.0000933
AC:
23
AN:
246628
Hom.:
0
AF XY:
0.0000451
AC XY:
6
AN XY:
133096
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00178
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000269
Gnomad OTH exome
AF:
0.000499
GnomAD4 exome
AF:
0.0000479
AC:
69
AN:
1441344
Hom.:
0
Cov.:
31
AF XY:
0.0000421
AC XY:
30
AN XY:
712614
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00176
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000137
Gnomad4 OTH exome
AF:
0.000152
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000204
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000906
AC:
11

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022CTCF: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;T;.;.;.;T;T;.;T
Eigen
Benign
-0.099
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.75
.;.;T;.;T;.;.;T;T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.035
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L;.;.;.;L;L;.;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.75
N;.;.;.;.;.;.;.;.
REVEL
Benign
0.074
Sift
Pathogenic
0.0
D;.;.;.;.;.;.;.;.
Sift4G
Benign
0.24
T;.;.;.;.;.;.;.;.
Polyphen
0.0
B;B;.;.;.;B;B;.;B
Vest4
0.43
MutPred
0.20
Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP
0.51
MPC
0.46
ClinPred
0.16
T
GERP RS
5.2
Varity_R
0.37
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766320761; hg19: chr16-67644866; API