Variant 14-105478782-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001312.4(CRIP2):c.248A>G(p.Glu83Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,428,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

CRIP2 (HGNC:2361): (cysteine rich protein 2) This gene encodes a putative transcription factor with two LIM zinc-binding domains. The encoded protein may participate in the differentiation of smooth muscle tissue. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

CRIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28227744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIP2	NM_001312.4 linkuse as main transcript	c.248A>G	p.Glu83Gly	missense_variant	4/8	ENST00000329146.9	NP_001303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIP2	ENST00000329146.9 linkuse as main transcript	c.248A>G	p.Glu83Gly	missense_variant	4/8	1	NM_001312.4	ENSP00000328521	P1	P52943-1

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150426

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1278124

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

621140

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150426

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73482

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

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

May 14, 2024

The c.248A>G (p.E83G) alteration is located in exon 4 (coding exon 4) of the CRIP2 gene. This alteration results from a A to G substitution at nucleotide position 248, causing the glutamic acid (E) at amino acid position 83 to be replaced by a glycine (G). 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

0.076

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.70

T;T

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.20

Sift

Benign

0.038

D;T

Sift4G

Benign

0.11

T;T

Polyphen

0.13

.;B

Vest4

0.22

MutPred

0.41

.;Gain of catalytic residue at L81 (P = 5e-04);

MVP

0.81

MPC

0.66

ClinPred

0.82

GERP RS

3.5

Varity_R

0.090

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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