18-50283881-C-T

Variant names:

• chr18-50283881-C-T
• rs3819217
• NM_014593.4:c.1413+13G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014593.4(CXXC1):​c.1413+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CXXC1 NM_014593.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 7 publications found

Genes affected

CXXC1 (HGNC:24343): (CXXC finger protein 1) This gene encodes a protein that functions as a transcriptional activator that binds specifically to non-methylated CpG motifs through its CXXC domain. The protein is a component of the SETD1 complex, regulates gene expression and is essential for vertebrate development. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXXC1	NM_014593.4	c.1413+13G>A		intron_variant	Intron 10 of 14	ENST00000285106.11	NP_055408.2
CXXC1	NM_001101654.2	c.1425+13G>A		intron_variant	Intron 10 of 14		NP_001095124.1
CXXC1	XM_011525940.3	c.1425+13G>A		intron_variant	Intron 11 of 15		XP_011524242.1
CXXC1	XM_017025718.3	c.1413+13G>A		intron_variant	Intron 11 of 15		XP_016881207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXXC1	ENST00000285106.11	c.1413+13G>A		intron_variant	Intron 10 of 14	1	NM_014593.4	ENSP00000285106.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.76

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: rs3819217; hg19: chr18-47810251;