3-3163840-A-G

Variant names:

• chr3-3163840-A-G
• rs711621
• NM_016302.4:c.687+3794T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016302.4(CRBN):​c.687+3794T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 152,208 control chromosomes in the GnomAD database, including 62,692 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 0.89 (62692 hom., cov: 33)
• Consequence: CRBN NM_016302.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 1 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]

CRBN Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 2

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• 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 rank	MANE	Protein	UniProt
CRBN	NM_016302.4	c.687+3794T>C		intron_variant	Intron 5 of 10	ENST00000231948.9	NP_057386.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRBN	ENST00000231948.9	c.687+3794T>C		intron_variant	Intron 5 of 10	1	NM_016302.4	ENSP00000231948.4

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135873 AN: 152090 Hom.: 62663 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.955

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: 0.922

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

GnomAD4 genome AF: 0.893 AC: 135956 AN: 152208 Hom.: 62692 Cov.: 33 AF XY: 0.898 AC XY: 66823 AN XY: 74420

African (AFR) AF: 0.633 AC: 26247 AN: 41460

American (AMR) AF: 0.955 AC: 14598 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3456 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5180

South Asian (SAS) AF: 0.998 AC: 4817 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10617 AN: 10618

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67894 AN: 68042

Other (OTH) AF: 0.922 AC: 1952 AN: 2116

Alfa AF: 0.938 Hom.: 8020

Bravo AF: 0.877

Asia WGS AF: 0.979 AC: 3404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs711621; hg19: chr3-3205524;