rs12593362

chr15-78342389-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRABP1	NM_004378.3	c.250-1110T>G		intron_variant		ENST00000299529.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRABP1	ENST00000299529.7	c.250-1110T>G		intron_variant		1	NM_004378.3	P1
CRABP1	ENST00000406419.1	c.317+1053T>G		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.572

Alfa AF: 0.663 Hom.: 22470

Bravo AF: 0.568

Asia WGS AF: 0.511 AC: 1775 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.95
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs12593362; hg19: chr15-78634731;