dbSNP rs73625090: CTCFL:c.-12+48T>A (chr20-57524980-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386993.1(CTCFL):c.-12+48T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 147,736 control chromosomes in the GnomAD database, including 118 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 0.037 ( 116 hom., cov: 29)

Exomes 𝑓: 0.024 ( 2 hom. )

Consequence

CTCFL
NM_001386993.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.28

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
CTCFL	NM_001386993.1	MANE Select	c.-12+48T>A	intron	N/A	NP_001373922.1	Q8NI51-1
CTCFL	NM_001269043.2		c.-12+48T>A	intron	N/A	NP_001255972.1	Q8NI51-7
CTCFL	NM_001269040.2		c.-12+494T>A	intron	N/A	NP_001255969.1	Q8NI51-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.-12+48T>A	intron	N/A	ENSP00000243914.3	Q8NI51-1
CTCFL	ENST00000423479.7	TSL:1	c.-12+48T>A	intron	N/A	ENSP00000415579.2	Q8NI51-7
CTCFL	ENST00000371196.6	TSL:1	c.-12+494T>A	intron	N/A	ENSP00000360239.2	Q8NI51-1

Frequencies

GnomAD3 genomes

AF:

0.0373

AC:

5434

AN:

145522

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0615

Gnomad AMI

AF:

0.0709

Gnomad AMR

AF:

0.0341

Gnomad ASJ

AF:

0.0316

Gnomad EAS

AF:

0.00458

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.0484

Gnomad NFE

AF:

0.0296

Gnomad OTH

AF:

0.0391

GnomAD4 exome

AF:

0.0243

AC:

AN:

2100

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

AN XY:

1076

show subpopulations

African (AFR)

AF:

0.133

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0435

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0214

AC:

AN:

1916

Other (OTH)

AF:

0.0278

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0374

AC:

5441

AN:

145636

Hom.:

116

Cov.:

AF XY:

0.0362

AC XY:

2575

AN XY:

71048

show subpopulations

African (AFR)

AF:

0.0616

AC:

2428

AN:

39426

American (AMR)

AF:

0.0339

AC:

501

AN:

14770

Ashkenazi Jewish (ASJ)

AF:

0.0316

AC:

108

AN:

3414

East Asian (EAS)

AF:

0.00459

AC:

AN:

4574

South Asian (SAS)

AF:

0.0369

AC:

159

AN:

4314

European-Finnish (FIN)

AF:

0.0105

AC:

100

AN:

9548

Middle Eastern (MID)

AF:

0.0486

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0296

AC:

1968

AN:

66376

Other (OTH)

AF:

0.0388

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

259

518

777

1036

1295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0302

Hom.:

Bravo

AF:

0.0388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.054

(source)

DANN

Benign

0.27

PhyloP100

-2.3

PromoterAI

0.057

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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