1-156700069-G-C

Variant names:

• chr1-156700069-G-C
• NM_001878.4:c.374C>G

Variant summary

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

The NM_001878.4(CRABP2):​c.374C>G​(p.Thr125Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T125M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRABP2 NM_001878.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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]

ENSG00000285570 (HGNC:):

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=0.11935738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRABP2	NM_001878.4	c.374C>G	p.Thr125Arg	missense_variant	Exon 4 of 4	ENST00000368222.8	NP_001869.1
CRABP2	NM_001199723.2	c.374C>G	p.Thr125Arg	missense_variant	Exon 5 of 5		NP_001186652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRABP2	ENST00000368222.8	c.374C>G	p.Thr125Arg	missense_variant	Exon 4 of 4	1	NM_001878.4	ENSP00000357205.3
CRABP2	ENST00000368221.1	c.374C>G	p.Thr125Arg	missense_variant	Exon 5 of 5	3		ENSP00000357204.1
CRABP2	ENST00000621784.4	c.374C>G	p.Thr125Arg	missense_variant	Exon 5 of 5	3		ENSP00000482841.1
ENSG00000285570	ENST00000650347.1	n.150-3882G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461280 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726870

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.21	T;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	.;T;.
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N;.;N
REVEL	Benign	0.068
Sift	Benign	0.50	T;.;T
Sift4G	Benign	0.67	T;T;T
Polyphen		0.031	B;B;B
Vest4		0.17
MutPred		0.44		Gain of solvent accessibility (P = 0.1505);Gain of solvent accessibility (P = 0.1505);Gain of solvent accessibility (P = 0.1505);
MVP		0.41
MPC		0.21
ClinPred		0.41	T
GERP RS		4.0
Varity_R		0.22
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156669861;