rs1669338

Positions:

• chr3-3157951-A-C
• chr3-3157951-A-G
• chr3-3157951-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016302.4(CRBN):​c.688-1670T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,084 control chromosomes in the GnomAD database, including 42,005 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (42005 hom., cov: 31)
• Consequence: CRBN NM_016302.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRBN	NM_016302.4	c.688-1670T>G		intron_variant		ENST00000231948.9	NP_057386.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRBN	ENST00000231948.9	c.688-1670T>G		intron_variant		1	NM_016302.4	ENSP00000231948.4

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109517 AN: 151966 Hom.: 42007 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.764

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.720 AC: 109537 AN: 152084 Hom.: 42005 Cov.: 31 AF XY: 0.725 AC XY: 53887 AN XY: 74344

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.765

Alfa AF: 0.818 Hom.: 67918

Bravo AF: 0.699

Asia WGS AF: 0.837 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs1669338; hg19: chr3-3199635;