NM_001878.4:c.366G>C

Variant names:

• chr1-156700542-C-G
• rs139634170
• NM_001878.4:c.366G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP3 BP6_Moderate BS2

The NM_001878.4(CRABP2):​c.366G>C​(p.Leu122Leu) variant causes a splice region, synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000843 in 1,612,502 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (2 hom.)
• Consequence: CRABP2 NM_001878.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.9951
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.54
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• BP6: Variant 1-156700542-C-G is Benign according to our data. Variant chr1-156700542-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 718267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001878.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRABP2	NM_001878.4	MANE Select	c.366G>C	p.Leu122Leu	splice_region synonymous	Exon 3 of 4	NP_001869.1	P29373
	CRABP2	NM_001199723.2		c.366G>C	p.Leu122Leu	splice_region synonymous	Exon 4 of 5	NP_001186652.1	P29373

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRABP2	ENST00000368222.8	TSL:1 MANE Select	c.366G>C	p.Leu122Leu	splice_region synonymous	Exon 3 of 4	ENSP00000357205.3	P29373
	CRABP2	ENST00000926911.1		c.390G>C	p.Leu130Leu	splice_region synonymous	Exon 3 of 4	ENSP00000596970.1
	CRABP2	ENST00000368221.1	TSL:3	c.366G>C	p.Leu122Leu	splice_region synonymous	Exon 4 of 5	ENSP00000357204.1	P29373

Frequencies

GnomAD3 genomes AF: 0.000756 AC: 115 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.00111 AC: 279 AN: 251416 AF XY: 0.00138

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00104

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000852 AC: 1244 AN: 1460248 Hom.: 2 Cov.: 31 AF XY: 0.00101 AC XY: 731 AN XY: 726592

African (AFR) AF: 0.000179 AC: 6 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00393 AC: 339 AN: 86222

European-Finnish (FIN) AF: 0.00142 AC: 76 AN: 53418

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5764

European-Non Finnish (NFE) AF: 0.000646 AC: 717 AN: 1110524

Other (OTH) AF: 0.00106 AC: 64 AN: 60332

GnomAD4 genome AF: 0.000755 AC: 115 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000766 AC XY: 57 AN XY: 74454

African (AFR) AF: 0.0000722 AC: 3 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4824

European-Finnish (FIN) AF: 0.00169 AC: 18 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68006

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.000465

Asia WGS AF: 0.00231 AC: 8 AN: 3476

EpiCase AF: 0.000872

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.92
PhyloP100		7.5
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.91
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

Other links and lift over

dbSNP: rs139634170; hg19: chr1-156670334; COSMIC: COSV107465940; COSMIC: COSV107465940;