Variant 1-156700542-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001878.4(CRABP2):c.366G>C(p.Leu122=) 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

Variant links:

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]

CRABP2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

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 id is 718267.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRABP2	NM_001878.4 linkuse as main transcript	c.366G>C	p.Leu122=	splice_region_variant, synonymous_variant	3/4	ENST00000368222.8	NP_001869.1
CRABP2	NM_001199723.2 linkuse as main transcript	c.366G>C	p.Leu122=	splice_region_variant, synonymous_variant	4/5		NP_001186652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CRABP2	ENST00000368222.8 linkuse as main transcript	c.366G>C	p.Leu122=	splice_region_variant, synonymous_variant	3/4	1	NM_001878.4	ENSP00000357205	P1
	ENST00000650347.1 linkuse as main transcript	n.150-3409C>G		intron_variant, non_coding_transcript_variant
CRABP2	ENST00000368221.1 linkuse as main transcript	c.366G>C	p.Leu122=	splice_region_variant, synonymous_variant	4/5	3		ENSP00000357204	P1
CRABP2	ENST00000621784.4 linkuse as main transcript	c.366G>C	p.Leu122=	splice_region_variant, synonymous_variant	4/5	3		ENSP00000482841	P1

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152136

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00111

AC:

279

AN:

251416

Hom.:

AF XY:

0.00138

AC XY:

188

AN XY:

135874

show subpopulations

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 SAS exome

AF:

0.00340

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.:

Cov.:

AF XY:

0.00101

AC XY:

731

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00393

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.000646

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152254

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.000465

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.000872

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.92

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

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