rs12593362

Variant names:

• chr15-78342389-T-G
• rs12593362
• NM_004378.3:c.250-1110T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004378.3(CRABP1):​c.250-1110T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,592 control chromosomes in the GnomAD database, including 26,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26881 hom., cov: 30)
• Consequence: CRABP1 NM_004378.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 11 publications found

Genes affected

CRABP1 (HGNC:2338): (cellular retinoic acid binding protein 1) This gene encodes a specific binding protein for a vitamin A family member and is thought to play an important role in retinoic acid-mediated differentiation and proliferation processes. It is structurally similar to the cellular retinol-binding proteins, but binds only retinoic acid at specific sites within the nucleus, which may contribute to vitamin A-directed differentiation in epithelial tissue. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004378.3. 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
	CRABP1	NM_004378.3	MANE Select	c.250-1110T>G		intron	N/A	NP_004369.1	F1T0F7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRABP1	ENST00000299529.7	TSL:1 MANE Select	c.250-1110T>G		intron	N/A	ENSP00000299529.6	P29762
	CRABP1	ENST00000923230.1		c.316-1110T>G		intron	N/A	ENSP00000593289.1
	CRABP1	ENST00000923231.1		c.298-1110T>G		intron	N/A	ENSP00000593290.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88195 AN: 151474 Hom.: 26874 Cov.: 30

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.573

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.582 AC: 88236 AN: 151592 Hom.: 26881 Cov.: 30 AF XY: 0.584 AC XY: 43274 AN XY: 74082

African (AFR) AF: 0.388 AC: 16009 AN: 41278

American (AMR) AF: 0.622 AC: 9480 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2057 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2652 AN: 5164

South Asian (SAS) AF: 0.620 AC: 2969 AN: 4790

European-Finnish (FIN) AF: 0.646 AC: 6773 AN: 10486

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46418 AN: 67862

Other (OTH) AF: 0.572 AC: 1203 AN: 2104

Alfa AF: 0.662 Hom.: 24710

Bravo AF: 0.568

Asia WGS AF: 0.511 AC: 1775 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.95
DANN	Benign	0.69
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12593362; hg19: chr15-78634731;