NM_001386993.1:c.148G>C

Variant names:

• chr20-57524058-C-G
• rs6070128
• NM_001386993.1:c.148G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386993.1(CTCFL):​c.148G>C​(p.Glu50Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,613,480 control chromosomes in the GnomAD database, including 125,868 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8850 hom., cov: 32)
  • Exomes 𝑓: 0.40 (117018 hom.)
• Consequence: CTCFL NM_001386993.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.810823E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	NM_001386993.1	MANE Select	c.148G>C	p.Glu50Gln	missense	Exon 2 of 11	NP_001373922.1
	CTCFL	NM_001269043.2		c.148G>C	p.Glu50Gln	missense	Exon 2 of 12	NP_001255972.1
	CTCFL	NM_001269044.3		c.148G>C	p.Glu50Gln	missense	Exon 1 of 10	NP_001255973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.148G>C	p.Glu50Gln	missense	Exon 2 of 11	ENSP00000243914.3
	CTCFL	ENST00000423479.7	TSL:1	c.148G>C	p.Glu50Gln	missense	Exon 2 of 12	ENSP00000415579.2
	CTCFL	ENST00000608440.5	TSL:1	c.148G>C	p.Glu50Gln	missense	Exon 1 of 10	ENSP00000477488.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48334 AN: 152004 Hom.: 8847 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.355

GnomAD2 exomes AF: 0.366 AC: 91818 AN: 251168 AF XY: 0.374

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.358

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.410

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.396 AC: 579227 AN: 1461358 Hom.: 117018 Cov.: 66 AF XY: 0.397 AC XY: 288726 AN XY: 726940

African (AFR) AF: 0.122 AC: 4094 AN: 33480

American (AMR) AF: 0.296 AC: 13233 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10972 AN: 26136

East Asian (EAS) AF: 0.341 AC: 13546 AN: 39700

South Asian (SAS) AF: 0.390 AC: 33681 AN: 86258

European-Finnish (FIN) AF: 0.368 AC: 19465 AN: 52934

Middle Eastern (MID) AF: 0.503 AC: 2901 AN: 5768

European-Non Finnish (NFE) AF: 0.412 AC: 457602 AN: 1111970

Other (OTH) AF: 0.393 AC: 23733 AN: 60388

GnomAD4 genome AF: 0.318 AC: 48326 AN: 152122 Hom.: 8850 Cov.: 32 AF XY: 0.319 AC XY: 23752 AN XY: 74354

African (AFR) AF: 0.130 AC: 5394 AN: 41526

American (AMR) AF: 0.331 AC: 5054 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1459 AN: 3466

East Asian (EAS) AF: 0.358 AC: 1851 AN: 5176

South Asian (SAS) AF: 0.377 AC: 1810 AN: 4804

European-Finnish (FIN) AF: 0.371 AC: 3927 AN: 10578

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27631 AN: 67968

Other (OTH) AF: 0.350 AC: 739 AN: 2112

Alfa AF: 0.351 Hom.: 3072

Bravo AF: 0.306

TwinsUK AF: 0.414 AC: 1534

ALSPAC AF: 0.401 AC: 1544

ESP6500AA AF: 0.128 AC: 565

ESP6500EA AF: 0.408 AC: 3513

ExAC AF: 0.364 AC: 44177

Asia WGS AF: 0.326 AC: 1135 AN: 3478

EpiCase AF: 0.416

EpiControl AF: 0.421

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.29
DANN	Benign	0.26
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.00038	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.14
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.0080
Sift	Benign	0.24	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.037
ClinPred		0.0032	T
GERP RS		-4.7
PromoterAI		-0.013	Neutral
Varity_R		0.072
gMVP		0.028
Mutation Taster		=100/0	polymorphism (auto)

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: rs6070128; hg19: chr20-56099114; COSMIC: COSV54772001;