rs10859563

chr12-93726563-C-Gchr12-93726563-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003805.5(CRADD):c.298+47491C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,942 control chromosomes in the GnomAD database, including 13,186 homozygotes. 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: 𝑓 0.41 (13186 hom., cov: 31)
• Consequence: CRADD NM_003805.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

Genes affected

CRADD (HGNC:2340): (CASP2 and RIPK1 domain containing adaptor with death domain) This gene encodes a protein containing a death domain (DD) motif. This protein recruits caspase 2/ICH1 to the cell death signal transduction complex, which includes tumor necrosis factor receptor 1 (TNFR1A) and RIPK1/RIP kinase, and acts in promoting apoptosis. A mutation in this gene was associated with cognitive disability. A related pseudogene is found on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CRADD-AS1 (HGNC:56184): (CRADD antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRADD	NM_003805.5	c.298+47491C>G		intron_variant		ENST00000332896.8
CRADD-AS1	NR_110092.1	n.294+9002G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRADD	ENST00000332896.8	c.298+47491C>G		intron_variant		1	NM_003805.5	P1
CRADD-AS1	ENST00000550287.1	n.294+9002G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62130 AN: 151824 Hom.: 13164 Cov.: 31

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62191 AN: 151942 Hom.: 13186 Cov.: 31 AF XY: 0.414 AC XY: 30724 AN XY: 74278

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.417

Alfa AF: 0.292 Hom.: 790

Bravo AF: 0.400

Asia WGS AF: 0.531 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.12
Dann	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs10859563; hg19: chr12-94120339;