Variant 3-3174046-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_016302.4(CRBN):c.377+13A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,606,866 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 32)

Exomes 𝑓: 0.013 ( 286 hom. )

Consequence

CRBN
NM_016302.4 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.100

Variant links:

Genes affected

CRBN (HGNC:30185): (cereblon) This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

CRBN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0118 (1797/152286) while in subpopulation SAS AF= 0.0307 (148/4828). AF 95% confidence interval is 0.0266. There are 33 homozygotes in gnomad4. There are 1053 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRBN	NM_016302.4 linkuse as main transcript	c.377+13A>C		intron_variant		ENST00000231948.9	NP_057386.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRBN	ENST00000231948.9 linkuse as main transcript	c.377+13A>C		intron_variant		1	NM_016302.4	ENSP00000231948	P4	Q96SW2-1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1797

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00884

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0308

Gnomad FIN

AF:

0.0577

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0170

AC:

4268

AN:

251286

Hom.:

AF XY:

0.0187

AC XY:

2534

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00523

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00272

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.0614

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0130

AC:

18885

AN:

1454580

Hom.:

286

Cov.:

AF XY:

0.0138

AC XY:

10022

AN XY:

724200

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00570

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.0392

Gnomad4 FIN exome

AF:

0.0581

Gnomad4 NFE exome

AF:

0.00970

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0118

AC:

1797

AN:

152286

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1053

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00882

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0307

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00704

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 17, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over