Variant 20-57524058-C-G 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.148G>C(p.Glu50Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,613,480 control chromosomes in the GnomAD database, including 125,868 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 0.32 ( 8850 hom., cov: 32)

Exomes 𝑓: 0.40 ( 117018 hom. )

Consequence

CTCFL
NM_001386993.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.139

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=3.810823E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 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.148G>C	p.Glu50Gln	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.148G>C	p.Glu50Gln	missense_variant	2/11	1	NM_001386993.1	ENSP00000243914.3		Q8NI51-1

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48334

AN:

152004

Hom.:

8847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.342

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.355

GnomAD3 exomes

AF:

0.366

AC:

91818

AN:

251168

Hom.:

17566

AF XY:

0.374

AC XY:

50802

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.358

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.393

GnomAD4 exome

AF:

0.396

AC:

579227

AN:

1461358

Hom.:

117018

Cov.:

AF XY:

0.397

AC XY:

288726

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.296

Gnomad4 ASJ exome

AF:

0.420

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.412

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.318

AC:

48326

AN:

152122

Hom.:

8850

Cov.:

AF XY:

0.319

AC XY:

23752

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.358

Gnomad4 SAS

AF:

0.377

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.351

Hom.:

3072

Bravo

AF:

0.306

TwinsUK

AF:

0.414

AC:

1534

ALSPAC

AF:

0.401

AC:

1544

ESP6500AA

AF:

0.128

AC:

565

ESP6500EA

AF:

0.408

AC:

3513

ExAC

AF:

0.364

AC:

44177

Asia WGS

AF:

0.326

AC:

1135

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.421

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.29

DANN

Benign

0.26

DEOGEN2

Benign

0.026

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

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.61

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

MetaRNN

Benign

0.00038

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

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

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

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.24

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

REVEL

Benign

0.0080

Sift

Benign

0.24

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

Sift4G

Benign

0.29

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

Polyphen

0.0

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

Vest4

0.021

MPC

0.037

ClinPred

0.0032

GERP RS

-4.7

Varity_R

0.072

gMVP

0.028

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