chr20-57508717-T-C

Variant names:

• chr20-57508717-T-C
• rs73625093
• NM_001386993.1:c.1563A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001386993.1(CTCFL):​c.1563A>G​(p.Lys521Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,614,176 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (8 hom.)
• Consequence: CTCFL NM_001386993.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-57508717-T-C is Benign according to our data. Variant chr20-57508717-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2652425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	NM_001386993.1	MANE Select	c.1563A>G	p.Lys521Lys	synonymous	Exon 9 of 11	NP_001373922.1
	CTCFL	NM_001269043.2		c.1563A>G	p.Lys521Lys	synonymous	Exon 9 of 12	NP_001255972.1
	CTCFL	NM_001269044.3		c.1563A>G	p.Lys521Lys	synonymous	Exon 8 of 10	NP_001255973.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.1563A>G	p.Lys521Lys	synonymous	Exon 9 of 11	ENSP00000243914.3
	CTCFL	ENST00000423479.7	TSL:1	c.1563A>G	p.Lys521Lys	synonymous	Exon 9 of 12	ENSP00000415579.2
	CTCFL	ENST00000608440.5	TSL:1	c.1563A>G	p.Lys521Lys	synonymous	Exon 8 of 10	ENSP00000477488.1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00165 AC: 415 AN: 251482 AF XY: 0.00175

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00242

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00179 AC: 2619 AN: 1461864 Hom.: 8 Cov.: 31 AF XY: 0.00188 AC XY: 1369 AN XY: 727232

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.00110 AC: 49 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 59 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00191 AC: 165 AN: 86256

European-Finnish (FIN) AF: 0.000412 AC: 22 AN: 53420

Middle Eastern (MID) AF: 0.00693 AC: 40 AN: 5768

European-Non Finnish (NFE) AF: 0.00193 AC: 2143 AN: 1111986

Other (OTH) AF: 0.00204 AC: 123 AN: 60396

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74486

African (AFR) AF: 0.000626 AC: 26 AN: 41560

American (AMR) AF: 0.00222 AC: 34 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4822

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00232 AC: 158 AN: 68036

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00212 Hom.: 0

Bravo AF: 0.00157

EpiCase AF: 0.00327

EpiControl AF: 0.00391

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.41
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73625093; hg19: chr20-56083773;