1-156700654-A-T

Position:

• chr1-156700654-A-T

Variant summary

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

The NM_001878.4(CRABP2):​c.254T>A​(p.Leu85Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRABP2 NM_001878.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.94

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]

(HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
CRABP2	NM_001878.4	c.254T>A	p.Leu85Gln	missense_variant	3/4	ENST00000368222.8	NP_001869.1
CRABP2	NM_001199723.2	c.254T>A	p.Leu85Gln	missense_variant	4/5		NP_001186652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRABP2	ENST00000368222.8	c.254T>A	p.Leu85Gln	missense_variant	3/4	1	NM_001878.4	ENSP00000357205	P1
	ENST00000650347.1	n.150-3297A>T		intron_variant, non_coding_transcript_variant
CRABP2	ENST00000368221.1	c.254T>A	p.Leu85Gln	missense_variant	4/5	3		ENSP00000357204	P1
CRABP2	ENST00000621784.4	c.254T>A	p.Leu85Gln	missense_variant	4/5	3		ENSP00000482841	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.254T>A (p.L85Q) alteration is located in exon 3 (coding exon 3) of the CRABP2 gene. This alteration results from a T to A substitution at nucleotide position 254, causing the leucine (L) at amino acid position 85 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	Benign	0.17
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T;T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D;.
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H;H;H
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.5	D;.;D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;.;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.34	B;B;B
Vest4		0.78
MutPred		0.54		Gain of disorder (P = 0.0292);Gain of disorder (P = 0.0292);Gain of disorder (P = 0.0292);
MVP		0.40
MPC		0.19
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.86
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-156670446;