12-93759028-T-C

Position:

• chr12-93759028-T-C

Variant summary

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

The NM_003805.5(CRADD):​c.298+79956T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,042 control chromosomes in the GnomAD database, including 10,928 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 0.35 (10928 hom., cov: 32)
• Consequence: CRADD NM_003805.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRADD	NM_003805.5	c.298+79956T>C		intron_variant		ENST00000332896.8	NP_003796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRADD	ENST00000332896.8	c.298+79956T>C		intron_variant		1	NM_003805.5	ENSP00000327647.3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53794 AN: 151924 Hom.: 10920 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.354 AC: 53819 AN: 152042 Hom.: 10928 Cov.: 32 AF XY: 0.358 AC XY: 26622 AN XY: 74314

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.368

Alfa AF: 0.409 Hom.: 12848

Bravo AF: 0.337

Asia WGS AF: 0.524 AC: 1815 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.78

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: rs1493848; hg19: chr12-94152804;