Genetic Variant CRABP2:p.Gly105Ser (chr1-156700595-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001878.4(CRABP2):c.313G>A(p.Gly105Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CRABP2
NM_001878.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRABP2	NM_001878.4 link	c.313G>A	p.Gly105Ser	missense_variant	Exon 3 of 4	ENST00000368222.8	NP_001869.1	P29373
CRABP2	NM_001199723.2 link	c.313G>A	p.Gly105Ser	missense_variant	Exon 4 of 5		NP_001186652.1	P29373

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRABP2	ENST00000368222.8 link	c.313G>A	p.Gly105Ser	missense_variant	Exon 3 of 4	1	NM_001878.4	ENSP00000357205.3	P29373
CRABP2	ENST00000368221.1 link	c.313G>A	p.Gly105Ser	missense_variant	Exon 4 of 5	3		ENSP00000357204.1	P29373
CRABP2	ENST00000621784.4 link	c.313G>A	p.Gly105Ser	missense_variant	Exon 4 of 5	3		ENSP00000482841.1	P29373
ENSG00000285570	ENST00000650347.1 link	n.150-3356C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727082

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.313G>A (p.G105S) alteration is located in exon 3 (coding exon 3) of the CRABP2 gene. This alteration results from a G to A substitution at nucleotide position 313, causing the glycine (G) at amino acid position 105 to be replaced by a serine (S). 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

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D;.

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

M;M;M

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-4.2

D;.;D

REVEL

Uncertain

0.40

Sift

Benign

0.063

T;.;T

Sift4G

Benign

0.062

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.62

MutPred

0.48

Gain of phosphorylation at G105 (P = 0.0422);Gain of phosphorylation at G105 (P = 0.0422);Gain of phosphorylation at G105 (P = 0.0422);

MVP

0.72

MPC

0.40

ClinPred

1.0

GERP RS

5.0

Varity_R

0.74

gMVP

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over