Variant 3-3174270-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016302.4(CRBN):c.175-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,600,996 control chromosomes in the GnomAD database, including 773,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 63343 hom., cov: 31)

Exomes 𝑓: 0.99 ( 710237 hom. )

Consequence

CRBN
NM_016302.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001158

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.116

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:

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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 3-3174270-A-G is Benign according to our data. Variant chr3-3174270-A-G is described in ClinVar as [Benign]. Clinvar id is 128855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-3174270-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRBN	NM_016302.4 linkuse as main transcript	c.175-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000231948.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRBN	ENST00000231948.9 linkuse as main transcript	c.175-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016302.4	P4	Q96SW2-1

Frequencies

GnomAD3 genomes

AF:

0.900

AC:

136852

AN:

152100

Hom.:

63314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.957

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.959

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.925

GnomAD3 exomes

AF:

0.972

AC:

244286

AN:

251212

Hom.:

119760

AF XY:

0.980

AC XY:

133107

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.642

Gnomad AMR exome

AF:

0.978

Gnomad ASJ exome

AF:

0.994

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.985

GnomAD4 exome

AF:

0.989

AC:

1432312

AN:

1448778

Hom.:

710237

Cov.:

AF XY:

0.990

AC XY:

714726

AN XY:

721786

show subpopulations

Gnomad4 AFR exome

AF:

0.638

Gnomad4 AMR exome

AF:

0.975

Gnomad4 ASJ exome

AF:

0.994

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.975

GnomAD4 genome

AF:

0.900

AC:

136937

AN:

152218

Hom.:

63343

Cov.:

AF XY:

0.904

AC XY:

67269

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.656

Gnomad4 AMR

AF:

0.957

Gnomad4 ASJ

AF:

0.995

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.998

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.926

Alfa

AF:

0.952

Hom.:

30030

Bravo

AF:

0.884

Asia WGS

AF:

0.980

AC:

3408

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 27, 2012

- -

Intellectual disability, autosomal recessive 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

5.2

Dann

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.070

SpliceAI score (max)

0.050

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