Variant 3-3174266-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016302.4(CRBN):c.175-5T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,588,214 control chromosomes in the GnomAD database, including 328 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 32)

Exomes 𝑓: 0.013 ( 295 hom. )

Consequence

CRBN
NM_016302.4 splice_region, intron

Scores

Splicing: ADA: 0.1779

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.478

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:

CRBN (HGNC:):

CRBN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 3-3174266-A-T is Benign according to our data. Variant chr3-3174266-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 128854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0118 (1796/152308) while in subpopulation SAS AF= 0.0309 (149/4820). AF 95% confidence interval is 0.0269. There are 33 homozygotes in gnomad4. There are 1052 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

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.175-5T>A		splice_region_variant, intron_variant		ENST00000231948.9	NP_057386.2	Q96SW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRBN	ENST00000231948.9 linkuse as main transcript	c.175-5T>A		splice_region_variant, intron_variant		1	NM_016302.4	ENSP00000231948.4		Q96SW2-1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1796

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0311

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:

4275

AN:

251172

Hom.:

AF XY:

0.0187

AC XY:

2538

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00524

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00272

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.0615

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0132

AC:

18939

AN:

1435906

Hom.:

295

Cov.:

AF XY:

0.0140

AC XY:

10053

AN XY:

716272

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.00573

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.00149

Gnomad4 SAS exome

AF:

0.0394

Gnomad4 FIN exome

AF:

0.0582

Gnomad4 NFE exome

AF:

0.00988

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0118

AC:

1796

AN:

152308

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1052

AN XY:

74460

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:

0.0309

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00704

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0100

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 17, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.8

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.18

dbscSNV1_RF

Benign

0.63

SpliceAI score (max)

0.12

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