Variant 20-57523677-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386993.1(CTCFL):c.529A>G(p.Thr177Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,613,034 control chromosomes in the GnomAD database, including 337,491 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.70 ( 38813 hom., cov: 33)

Exomes 𝑓: 0.64 ( 298678 hom. )

Consequence

CTCFL
NM_001386993.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.28

Variant links:

Genes affected

CTCFL (HGNC:16234): (CCCTC-binding factor like) CCCTC-binding factor (CTCF), an 11-zinc-finger factor involved in gene regulation, utilizes different zinc fingers to bind varying DNA target sites. CTCF forms methylation-sensitive insulators that regulate X-chromosome inactivation. This gene is a paralog of CTCF and appears to be expressed primarily in the cytoplasm of spermatocytes, unlike CTCF which is expressed primarily in the nucleus of somatic cells. CTCF and the protein encoded by this gene are normally expressed in a mutually exclusive pattern that correlates with resetting of methylation marks during male germ cell differentiation. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

CTCFL links:

CTCFL (HGNC:):

CTCFL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0147996E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTCFL	NM_001386993.1 linkuse as main transcript	c.529A>G	p.Thr177Ala	missense_variant	2/11	ENST00000243914.8	NP_001373922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTCFL	ENST00000243914.8 linkuse as main transcript	c.529A>G	p.Thr177Ala	missense_variant	2/11	1	NM_001386993.1	ENSP00000243914.3		Q8NI51-1

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106982

AN:

152080

Hom.:

38774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.535

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.739

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.720

GnomAD3 exomes

AF:

0.656

AC:

163185

AN:

248616

Hom.:

54232

AF XY:

0.651

AC XY:

87546

AN XY:

134574

show subpopulations

Gnomad AFR exome

AF:

0.890

Gnomad AMR exome

AF:

0.650

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.735

Gnomad SAS exome

AF:

0.648

Gnomad FIN exome

AF:

0.561

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.649

GnomAD4 exome

AF:

0.637

AC:

931083

AN:

1460836

Hom.:

298678

Cov.:

AF XY:

0.637

AC XY:

462573

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.897

Gnomad4 AMR exome

AF:

0.654

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.733

Gnomad4 SAS exome

AF:

0.647

Gnomad4 FIN exome

AF:

0.566

Gnomad4 NFE exome

AF:

0.626

Gnomad4 OTH exome

AF:

0.660

GnomAD4 genome

AF:

0.703

AC:

107071

AN:

152198

Hom.:

38813

Cov.:

AF XY:

0.699

AC XY:

52042

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.885

Gnomad4 AMR

AF:

0.676

Gnomad4 ASJ

AF:

0.656

Gnomad4 EAS

AF:

0.738

Gnomad4 SAS

AF:

0.658

Gnomad4 FIN

AF:

0.559

Gnomad4 NFE

AF:

0.625

Gnomad4 OTH

AF:

0.724

Alfa

AF:

0.646

Hom.:

64493

Bravo

AF:

0.722

TwinsUK

AF:

0.626

AC:

2323

ALSPAC

AF:

0.623

AC:

2400

ESP6500AA

AF:

0.877

AC:

3866

ESP6500EA

AF:

0.632

AC:

5431

ExAC

AF:

0.662

AC:

80327

Asia WGS

AF:

0.687

AC:

2391

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0020

DANN

Benign

0.38

DEOGEN2

Benign

0.044

.;T;T;.;T;T;.;.;.;.;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.10

T;.;.;T;.;T;T;T;T;T;.;T

MetaRNN

Benign

0.0000010

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;N;N;N;N;N;N;N;N;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.88

N;.;.;N;N;N;.;N;N;.;.;.

REVEL

Benign

0.013

Sift

Benign

0.56

T;.;.;T;T;T;.;T;T;.;.;.

Sift4G

Benign

0.74

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;B;B;.;B;B;.;.;.;.;.;.

Vest4

0.0090

MPC

0.036

ClinPred

0.0067

GERP RS

-6.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.061

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over