rs6070122

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001386993.1(CTCFL):c.1573C>G(p.Gln525Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,614,114 control chromosomes in the GnomAD database, including 519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 38 hom., cov: 32)

Exomes 𝑓: 0.023 ( 481 hom. )

Consequence

CTCFL
NM_001386993.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.77

Publications

11 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054570436).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.018 (2745/152280) while in subpopulation NFE AF = 0.0253 (1719/68018). AF 95% confidence interval is 0.0243. There are 38 homozygotes in GnomAd4. There are 1418 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 38 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386993.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTCFL	NM_001386993.1	MANE Select	c.1573C>G	p.Gln525Glu	missense	Exon 9 of 11	NP_001373922.1	Q8NI51-1
CTCFL	NM_001269043.2		c.1573C>G	p.Gln525Glu	missense	Exon 9 of 12	NP_001255972.1	Q8NI51-7
CTCFL	NM_001269044.3		c.1573C>G	p.Gln525Glu	missense	Exon 8 of 10	NP_001255973.1	Q8NI51-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.1573C>G	p.Gln525Glu	missense	Exon 9 of 11	ENSP00000243914.3	Q8NI51-1
CTCFL	ENST00000423479.7	TSL:1	c.1573C>G	p.Gln525Glu	missense	Exon 9 of 12	ENSP00000415579.2	Q8NI51-7
CTCFL	ENST00000608440.5	TSL:1	c.1573C>G	p.Gln525Glu	missense	Exon 8 of 10	ENSP00000477488.1	Q8NI51-3

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2745

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.0612

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0253

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0197

AC:

4942

AN:

251474

AF XY:

0.0198

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.00674

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0544

Gnomad NFE exome

AF:

0.0260

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0230

AC:

33686

AN:

1461834

Hom.:

481

Cov.:

AF XY:

0.0225

AC XY:

16337

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00332

AC:

111

AN:

33478

American (AMR)

AF:

0.00671

AC:

300

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

315

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00927

AC:

800

AN:

86258

European-Finnish (FIN)

AF:

0.0555

AC:

2963

AN:

53420

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0252

AC:

28040

AN:

1111958

Other (OTH)

AF:

0.0186

AC:

1122

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1662

3324

4986

6648

8310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

996

1992

2988

3984

4980

<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:

0.0180

AC:

2745

AN:

152280

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1418

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00327

AC:

136

AN:

41562

American (AMR)

AF:

0.00713

AC:

109

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00767

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0612

AC:

649

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0253

AC:

1719

AN:

68018

Other (OTH)

AF:

0.0133

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

139

278

417

556

695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0222

Hom.:

Bravo

AF:

0.0133

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0242

AC:

208

ExAC

AF:

0.0197

AC:

2394

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0226

EpiControl

AF:

0.0234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.6

PhyloP100

7.8

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.28

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.24

MPC

1.5

ClinPred

0.016

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.54

gMVP

0.18

Mutation Taster

=98/2

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

Computational scores

Splicing

Publications

Other links and lift over