1-156700033-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001878.4(CRABP2):c.410G>A(p.Arg137Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

CRABP2
NM_001878.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

Variant links:

Genes affected

CRABP2 (HGNC:2339): (cellular retinoic acid binding protein 2) This gene encodes a member of the retinoic acid (RA, a form of vitamin A) binding protein family and lipocalin/cytosolic fatty-acid binding protein family. The protein is a cytosol-to-nuclear shuttling protein, which facilitates RA binding to its cognate receptor complex and transfer to the nucleus. It is involved in the retinoid signaling pathway, and is associated with increased circulating low-density lipoprotein cholesterol. Alternatively spliced transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2010]

CRABP2 links:

ENSG00000285570 (HGNC:):

ENSG00000285570 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40430993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRABP2	NM_001878.4 link	c.410G>A	p.Arg137Gln	missense_variant	Exon 4 of 4	ENST00000368222.8	NP_001869.1	P29373
CRABP2	NM_001199723.2 link	c.410G>A	p.Arg137Gln	missense_variant	Exon 5 of 5		NP_001186652.1	P29373

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRABP2	ENST00000368222.8 link	c.410G>A	p.Arg137Gln	missense_variant	Exon 4 of 4	1	NM_001878.4	ENSP00000357205.3	P29373
CRABP2	ENST00000368221.1 link	c.410G>A	p.Arg137Gln	missense_variant	Exon 5 of 5	3		ENSP00000357204.1	P29373
CRABP2	ENST00000621784.4 link	c.410G>A	p.Arg137Gln	missense_variant	Exon 5 of 5	3		ENSP00000482841.1	P29373
ENSG00000285570	ENST00000650347.1 link	n.150-3918C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000562

AC:

AN:

249246

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134770

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000988

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000622

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1461002

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410G>A (p.R137Q) alteration is located in exon 4 (coding exon 4) of the CRABP2 gene. This alteration results from a G to A substitution at nucleotide position 410, causing the arginine (R) at amino acid position 137 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

T;T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

.;T;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.6

H;H;H

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.4

N;.;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.012

D;.;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.29

MVP

0.55

MPC

0.69

ClinPred

0.87

GERP RS

4.1

Varity_R

0.74

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over