chr12-93864420-T-C

Position:

• chr12-93864420-T-C

Variant summary

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

The NM_001320100.2(CRADD):​c.299-29630T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,080 control chromosomes in the GnomAD database, including 11,546 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 0.37 (11546 hom., cov: 32)
• Consequence: CRADD NM_001320100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRADD	NM_001320100.2	c.299-29630T>C		intron_variant
CRADD	NR_135147.2	n.526+4978T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRADD	ENST00000548483.5	c.299-29630T>C		intron_variant		2
CRADD	ENST00000551065.5	c.*110+4978T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56804 AN: 151962 Hom.: 11545 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.374 AC: 56832 AN: 152080 Hom.: 11546 Cov.: 32 AF XY: 0.370 AC XY: 27531 AN XY: 74356

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.373

Alfa AF: 0.441 Hom.: 19787

Bravo AF: 0.361

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4275668; hg19: chr12-94258196;