Variant 15-78347972-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004378.3(CRABP1):c.409G>C(p.Glu137Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000582 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 1 hom. )

Consequence

CRABP1
NM_004378.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

Variant links:

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]

CRABP1 links:

CRABP1 (HGNC:):

CRABP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037321717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRABP1	NM_004378.3 linkuse as main transcript	c.409G>C	p.Glu137Gln	missense_variant	4/4	ENST00000299529.7	NP_004369.1	P29762F1T0F7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRABP1	ENST00000299529.7 linkuse as main transcript	c.409G>C	p.Glu137Gln	missense_variant	4/4	1	NM_004378.3	ENSP00000299529.6	P29762
CRABP1	ENST00000406419.1 linkuse as main transcript	n.*137G>C		non_coding_transcript_exon_variant	4/4	5		ENSP00000385978.1	B5MCB5
CRABP1	ENST00000560753.1 linkuse as main transcript	n.152G>C		non_coding_transcript_exon_variant	1/1	6
CRABP1	ENST00000406419.1 linkuse as main transcript	n.*137G>C		3_prime_UTR_variant	4/4	5		ENSP00000385978.1	B5MCB5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251362

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727212

show subpopulations

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:

0.000997

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.409G>C (p.E137Q) alteration is located in exon 4 (coding exon 4) of the CRABP1 gene. This alteration results from a G to C substitution at nucleotide position 409, causing the glutamic acid (E) at amino acid position 137 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

0.30

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0080

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.67

REVEL

Benign

0.040

Sift

Benign

0.096

Sift4G

Benign

0.10

Polyphen

0.043

Vest4

0.24

MutPred

0.47

Loss of disorder (P = 0.1829);

MVP

0.10

MPC

0.87

ClinPred

0.092

GERP RS

4.4

Varity_R

0.12

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over