rs4183

Variant names:

• chr3-3150840-A-ATAAC
• rs4183
• ENST00000488263.5:n.3695_3698dupGTTA

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000488263.5(CRBN):​n.3695_3698dupGTTA variant causes a non coding transcript exon 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 ENST00000488263.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710
• Publications: 17 publications found

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]

TRNT1 Gene-Disease associations (from GenCC):

• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• retinitis pigmentosa and erythrocytic microcytosis

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CRBN	NM_016302.4	c.*21_*24dupGTTA		3_prime_UTR_variant	Exon 11 of 11	ENST00000231948.9	NP_057386.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRBN	ENST00000231948.9	c.*21_*24dupGTTA		3_prime_UTR_variant	Exon 11 of 11	1	NM_016302.4	ENSP00000231948.4

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

GnomAD2 exomes AF: 0.532 AC: 126651 AN: 238242 AF XY: 0.546

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 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

African (AFR) AF: 0.321 AC: 10628 AN: 33154

American (AMR) AF: 0.369 AC: 16238 AN: 44050

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 18061 AN: 25932

East Asian (EAS) AF: 0.183 AC: 7225 AN: 39420

South Asian (SAS) AF: 0.472 AC: 40229 AN: 85302

European-Finnish (FIN) AF: 0.577 AC: 30509 AN: 52862

Middle Eastern (MID) AF: 0.688 AC: 3946 AN: 5738

European-Non Finnish (NFE) AF: 0.668 AC: 737374 AN: 1103090

Other (OTH) AF: 0.607 AC: 36295 AN: 59816

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

African (AFR) AF: 0.338 AC: 14013 AN: 41410

American (AMR) AF: 0.483 AC: 7356 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2458 AN: 3458

East Asian (EAS) AF: 0.199 AC: 1025 AN: 5162

South Asian (SAS) AF: 0.442 AC: 2130 AN: 4820

European-Finnish (FIN) AF: 0.565 AC: 5928 AN: 10484

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.668 AC: 45299 AN: 67838

Other (OTH) AF: 0.590 AC: 1248 AN: 2114

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

Mar 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.071
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4183; hg19: chr3-3192524; COSMIC: COSV51640498; COSMIC: COSV51640498;