rs4183

Positions:

• chr3-3150840-A-ATAAC
• chr3-3150840-A-ATAACTAAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016302.4(CRBN):​c.*24_*25insGTTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,601,088 control chromosomes in the GnomAD database, including 313,500 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (23172 hom., cov: 0)
  • Exomes 𝑓: 0.62 (290328 hom.)
• Consequence: CRBN NM_016302.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710

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]

TRNT1 (HGNC:17341): (tRNA nucleotidyl transferase 1) The protein encoded by this gene is a CCA-adding enzyme which belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family. This essential enzyme functions by catalyzing the addition of the conserved nucleotide triplet CCA to the 3' terminus of tRNA molecules. Mutations in this gene result in sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-3150840-A-ATAAC is Benign according to our data. Variant chr3-3150840-A-ATAAC is described in ClinVar as [Benign]. Clinvar id is 1277739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRBN	NM_016302.4	c.*24_*25insGTTA		3_prime_UTR_variant	11/11	ENST00000231948.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRBN	ENST00000231948.9	c.*24_*25insGTTA		3_prime_UTR_variant	11/11	1	NM_016302.4	P4

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80331 AN: 151606 Hom.: 23181 Cov.: 0

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.590

GnomAD3 exomes AF: 0.532 AC: 126651 AN: 238242 Hom.: 36801 AF XY: 0.546 AC XY: 70200 AN XY: 128582

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.212

Gnomad SAS exome AF: 0.466

Gnomad FIN exome AF: 0.568

Gnomad NFE exome AF: 0.665

Gnomad OTH exome AF: 0.603

GnomAD4 exome AF: 0.621 AC: 900505 AN: 1449364 Hom.: 290328 Cov.: 31 AF XY: 0.620 AC XY: 446811 AN XY: 720594

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.668

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.529 AC: 80327 AN: 151724 Hom.: 23172 Cov.: 0 AF XY: 0.520 AC XY: 38507 AN XY: 74122

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.590

Alfa AF: 0.598 Hom.: 5053

Bravo AF: 0.513

Asia WGS AF: 0.344 AC: 1199 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 28, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4183; hg19: chr3-3192524;