rs757719993

Positions:

• chr3-3179681-C-A
• chr3-3179681-C-G
• chr3-3179681-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016302.4(CRBN):​c.7G>T​(p.Gly3Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CRBN NM_016302.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25015724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRBN	NM_016302.4	c.7G>T	p.Gly3Cys	missense_variant	1/11	ENST00000231948.9	NP_057386.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRBN	ENST00000231948.9	c.7G>T	p.Gly3Cys	missense_variant	1/11	1	NM_016302.4	ENSP00000231948	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247536 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134382

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.023	.;T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.0	.;N;N
MutationTaster	Benign	0.96	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.75	.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.020	.;D;D
Sift4G	Benign	0.097	.;T;T
Polyphen		0.97, 0.98	.;D;D
Vest4		0.34, 0.36
MutPred		0.23		Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);
MVP		0.69
MPC		0.13
ClinPred		0.78	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.43

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: rs757719993; hg19: chr3-3221365;