chr18-50283881-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014593.4(CXXC1):​c.1413+13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,646 control chromosomes in the GnomAD database, including 91,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8534 hom., cov: 33)
  • Exomes 𝑓: 0.33 (83208 hom.)
• Consequence: CXXC1 NM_014593.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 18-50283881-C-G is Benign according to our data. Variant chr18-50283881-C-G is described in ClinVar as Benign. ClinVar VariationId is 1222106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXXC1	NM_014593.4	c.1413+13G>C		intron_variant	Intron 10 of 14	ENST00000285106.11	NP_055408.2
CXXC1	NM_001101654.2	c.1425+13G>C		intron_variant	Intron 10 of 14		NP_001095124.1
CXXC1	XM_011525940.3	c.1425+13G>C		intron_variant	Intron 11 of 15		XP_011524242.1
CXXC1	XM_017025718.3	c.1413+13G>C		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>C		intron_variant	Intron 10 of 14	1	NM_014593.4	ENSP00000285106.6

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49198 AN: 152066 Hom.: 8519 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.382 AC: 96000 AN: 251310 AF XY: 0.379

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.618

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.329 AC: 481225 AN: 1461462 Hom.: 83208 Cov.: 42 AF XY: 0.332 AC XY: 241490 AN XY: 727042

African (AFR) AF: 0.244 AC: 8172 AN: 33470

American (AMR) AF: 0.540 AC: 24132 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 10158 AN: 26136

East Asian (EAS) AF: 0.594 AC: 23556 AN: 39690

South Asian (SAS) AF: 0.436 AC: 37596 AN: 86248

European-Finnish (FIN) AF: 0.287 AC: 15313 AN: 53356

Middle Eastern (MID) AF: 0.364 AC: 2102 AN: 5768

European-Non Finnish (NFE) AF: 0.306 AC: 339724 AN: 1111700

Other (OTH) AF: 0.339 AC: 20472 AN: 60370

GnomAD4 genome AF: 0.324 AC: 49241 AN: 152184 Hom.: 8534 Cov.: 33 AF XY: 0.327 AC XY: 24346 AN XY: 74402

African (AFR) AF: 0.249 AC: 10325 AN: 41498

American (AMR) AF: 0.454 AC: 6950 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3148 AN: 5178

South Asian (SAS) AF: 0.444 AC: 2140 AN: 4822

European-Finnish (FIN) AF: 0.280 AC: 2966 AN: 10592

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21291 AN: 68006

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.243 Hom.: 881

Bravo AF: 0.336

Asia WGS AF: 0.503 AC: 1747 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.78
DANN	Benign	0.64
PhyloP100		-0.76
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: rs3819217; hg19: chr18-47810251; COSMIC: COSV53274049; COSMIC: COSV53274049;