Genetic Variant NM_001386993.1:c.-12+117A>G (chr20-57524911-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001386993.1(CTCFL):c.-12+117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000012 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTCFL
NM_001386993.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.570

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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
CTCFL	NM_001386993.1	MANE Select	c.-12+117A>G	intron	N/A	NP_001373922.1
CTCFL	NM_001269043.2		c.-12+117A>G	intron	N/A	NP_001255972.1
CTCFL	NM_001269040.2		c.-12+563A>G	intron	N/A	NP_001255969.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.-12+117A>G	intron	N/A	ENSP00000243914.3
CTCFL	ENST00000423479.7	TSL:1	c.-12+117A>G	intron	N/A	ENSP00000415579.2
CTCFL	ENST00000371196.6	TSL:1	c.-12+563A>G	intron	N/A	ENSP00000360239.2

Frequencies

GnomAD3 genomes

AF:

0.0000123

AC:

AN:

81132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000460

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

113178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

53820

African (AFR)

AF:

0.00

AC:

AN:

2056

American (AMR)

AF:

0.00

AC:

AN:

126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

728

East Asian (EAS)

AF:

0.00

AC:

AN:

480

South Asian (SAS)

AF:

0.00

AC:

AN:

2306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

103600

Other (OTH)

AF:

0.00

AC:

AN:

3622

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000123

AC:

AN:

81172

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

39782

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000459

AC:

AN:

21788

American (AMR)

AF:

0.00

AC:

AN:

8606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2032

East Asian (EAS)

AF:

0.00

AC:

AN:

3018

South Asian (SAS)

AF:

0.00

AC:

AN:

2262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

37510

Other (OTH)

AF:

0.00

AC:

AN:

1232

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.41

(source)

DANN

Benign

0.59

PhyloP100

-0.57

PromoterAI

-0.063

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over