Variant 4-104491452-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_025212.4(CXXC4):c.351T>G(p.Gly117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 789,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

CXXC4
NM_025212.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0100

Variant links:

Genes affected

CXXC4 (HGNC:24593): (CXXC finger protein 4) This gene encodes a CXXC-type zinc finger domain-containing protein that functions as an antagonist of the canonical wingless/integrated signaling pathway. The encoded protein negatively regulates wingless/integrated signaling through interaction with the post synaptic density protein/ Drosophila disc large tumor suppressor/ zonula occludens-1 protein domain of Dishevelled, a scaffolding protein required for the stabilization of the transcriptional co-activator beta-catenin. In addition, the CXXC domain of this protein has been shown to bind unmethylated CpG dinucleotides, localize to promoters and CpG islands, and interact with the catalytic domain of methylcytosine dioxygenase ten-eleven-translocation 2, an iron and alpha-ketoglutarate-dependent dioxygenase that modifies the methylation status of DNA. In humans, a mutation in this gene has been associated with development of malignant renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

CXXC4 links:

CXXC4-AS1 (HGNC:41054): (CXXC4 antisense RNA 1)

CXXC4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-104491452-A-C is Benign according to our data. Variant chr4-104491452-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2654993.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.01 with no splicing effect.

BS2

High AC in GnomAd4 at 66 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CXXC4	NM_025212.4 linkuse as main transcript	c.351T>G	p.Gly117=	synonymous_variant	2/3	ENST00000394767.3
CXXC4-AS1	NR_125926.1 linkuse as main transcript	n.96+392A>C		intron_variant, non_coding_transcript_variant
CXXC4	XM_011532284.3 linkuse as main transcript	c.351T>G	p.Gly117=	synonymous_variant	3/4
CXXC4	NR_132741.2 linkuse as main transcript	n.270+3054T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXXC4	ENST00000394767.3 linkuse as main transcript	c.351T>G	p.Gly117=	synonymous_variant	2/3	5	NM_025212.4	P2
CXXC4-AS1	ENST00000500179.1 linkuse as main transcript	n.96+392A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

112444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000419

Gnomad ASJ

AF:

0.000352

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00211

Gnomad FIN

AF:

0.000711

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000226

Gnomad OTH

AF:

0.00130

GnomAD4 exome

AF:

0.0000901

AC:

AN:

677090

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

321552

show subpopulations

Gnomad4 AFR exome

AF:

0.000462

Gnomad4 AMR exome

AF:

0.000277

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000877

Gnomad4 OTH exome

AF:

0.0000800

GnomAD4 genome

AF:

0.000587

AC:

AN:

112488

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

AN XY:

54490

show subpopulations

Gnomad4 AFR

AF:

0.00102

Gnomad4 AMR

AF:

0.000419

Gnomad4 ASJ

AF:

0.000352

Gnomad4 EAS

AF:

0.00118

Gnomad4 SAS

AF:

0.00246

Gnomad4 FIN

AF:

0.000711

Gnomad4 NFE

AF:

0.000226

Gnomad4 OTH

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

CXXC4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.1

DANN

Benign

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over