rs373145132

Variant names:

• chr3-3167667-T-A
• NM_016302.4:c.654A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-3167667-T-A
• chr3-3167667-T-C

Variant summary

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

The NM_016302.4(CRBN):​c.654A>T​(p.Gln218His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 32)
• Consequence: CRBN NM_016302.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879

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=0.13354275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRBN	NM_016302.4	c.654A>T	p.Gln218His	missense_variant	Exon 5 of 11	ENST00000231948.9	NP_057386.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRBN	ENST00000231948.9	c.654A>T	p.Gln218His	missense_variant	Exon 5 of 11	1	NM_016302.4	ENSP00000231948.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.70
DEOGEN2	Benign	0.023	.;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	.;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.49	.;N;N
REVEL	Benign	0.11
Sift	Benign	0.12	.;T;T
Sift4G	Benign	0.55	.;T;T
Polyphen		0.77, 0.73	.;P;P
Vest4		0.26, 0.26
MutPred		0.42		Gain of glycosylation at S214 (P = 0.0288);Gain of glycosylation at S214 (P = 0.0288);.;
MVP		0.67
MPC		0.081
ClinPred		0.23	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.058
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-3209351;