1-156700589-T-C

Position:

chr1-156700589-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001878.4(CRABP2):c.319A>G(p.Lys107Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,708 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

CRABP2
NM_001878.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10702187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRABP2	NM_001878.4 linkuse as main transcript	c.319A>G	p.Lys107Glu	missense_variant	3/4	ENST00000368222.8	NP_001869.1	P29373
CRABP2	NM_001199723.2 linkuse as main transcript	c.319A>G	p.Lys107Glu	missense_variant	4/5		NP_001186652.1	P29373

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRABP2	ENST00000368222.8 linkuse as main transcript	c.319A>G	p.Lys107Glu	missense_variant	3/4	1	NM_001878.4	ENSP00000357205.3	P29373
CRABP2	ENST00000368221.1 linkuse as main transcript	c.319A>G	p.Lys107Glu	missense_variant	4/5	3		ENSP00000357204.1	P29373
CRABP2	ENST00000621784.4 linkuse as main transcript	c.319A>G	p.Lys107Glu	missense_variant	4/5	3		ENSP00000482841.1	P29373
ENSG00000285570	ENST00000650347.1 linkuse as main transcript	n.150-3362T>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000994

AC:

AN:

251434

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1461562

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.319A>G (p.K107E) alteration is located in exon 3 (coding exon 3) of the CRABP2 gene. This alteration results from a A to G substitution at nucleotide position 319, causing the lysine (K) at amino acid position 107 to be replaced by a glutamic acid (E). 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

Benign

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Benign

0.80

DEOGEN2

Benign

0.095

T;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

.;D;.

M_CAP

Benign

0.0089

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

N;N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.21

N;.;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;.;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.66

MutPred

0.42

Loss of ubiquitination at K107 (P = 0.0155);Loss of ubiquitination at K107 (P = 0.0155);Loss of ubiquitination at K107 (P = 0.0155);

MVP

0.51

MPC

0.22

ClinPred

0.071

GERP RS

5.0

Varity_R

0.59

gMVP

0.65

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

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