dbSNP rs6025601: CTCFL:p.Asp381Asp (chr20-57515751-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001386993.1(CTCFL):c.1143T>C(p.Asp381Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,613,644 control chromosomes in the GnomAD database, including 38,820 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 0.26 ( 5588 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33232 hom. )

Consequence

CTCFL
NM_001386993.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

16 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=1.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTCFL	NM_001386993.1 link	c.1143T>C	p.Asp381Asp	synonymous_variant	Exon 6 of 11	ENST00000243914.8	NP_001373922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTCFL	ENST00000243914.8 link	c.1143T>C	p.Asp381Asp	synonymous_variant	Exon 6 of 11	1	NM_001386993.1	ENSP00000243914.3		Q8NI51-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39175

AN:

151850

Hom.:

5574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.256

GnomAD2 exomes

AF:

0.240

AC:

60374

AN:

251408

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.207

AC:

302750

AN:

1461676

Hom.:

33232

Cov.:

AF XY:

0.207

AC XY:

150619

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.369

AC:

12353

AN:

33474

American (AMR)

AF:

0.317

AC:

14164

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5208

AN:

26130

East Asian (EAS)

AF:

0.369

AC:

14638

AN:

39696

South Asian (SAS)

AF:

0.238

AC:

20569

AN:

86244

European-Finnish (FIN)

AF:

0.187

AC:

9963

AN:

53394

Middle Eastern (MID)

AF:

0.181

AC:

1041

AN:

5766

European-Non Finnish (NFE)

AF:

0.190

AC:

211705

AN:

1111872

Other (OTH)

AF:

0.217

AC:

13109

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

12434

24868

37302

49736

62170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7652

15304

22956

30608

38260

<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:

0.258

AC:

39232

AN:

151968

Hom.:

5588

Cov.:

AF XY:

0.257

AC XY:

19115

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.370

AC:

15330

AN:

41414

American (AMR)

AF:

0.275

AC:

4201

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

703

AN:

3468

East Asian (EAS)

AF:

0.374

AC:

1930

AN:

5156

South Asian (SAS)

AF:

0.258

AC:

1243

AN:

4812

European-Finnish (FIN)

AF:

0.176

AC:

1862

AN:

10552

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13167

AN:

67986

Other (OTH)

AF:

0.263

AC:

556

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1469

2938

4407

5876

7345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.222

Hom.:

14201

Bravo

AF:

0.272

Asia WGS

AF:

0.329

AC:

1142

AN:

3478

EpiCase

AF:

0.197

EpiControl

AF:

0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.7

(source)

DANN

Benign

0.50

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=67/33

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over