Genetic Variant CRIP2:p.Pro85Leu (chr14-105478788-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001312.4(CRIP2):c.254C>T(p.Pro85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,432,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P85Q) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09028199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIP2	NM_001312.4 link	c.254C>T	p.Pro85Leu	missense_variant	Exon 4 of 8	ENST00000329146.9	NP_001303.1	P52943-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIP2	ENST00000329146.9 link	c.254C>T	p.Pro85Leu	missense_variant	Exon 4 of 8	1	NM_001312.4	ENSP00000328521.5		P52943-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151740

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000211

AC:

AN:

47474

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000159

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000312

AC:

AN:

1281024

Hom.:

Cov.:

AF XY:

0.00000321

AC XY:

AN XY:

622978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26582

American (AMR)

AF:

0.00

AC:

AN:

19144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18640

East Asian (EAS)

AF:

0.0000598

AC:

AN:

33472

South Asian (SAS)

AF:

0.00

AC:

AN:

62512

European-Finnish (FIN)

AF:

0.0000322

AC:

AN:

31092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3586

European-Non Finnish (NFE)

AF:

9.68e-7

AC:

AN:

1032908

Other (OTH)

AF:

0.00

AC:

AN:

53088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151740

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41326

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67886

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.82

T;T

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

.;M

PhyloP100

0.10

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.092

Sift

Benign

0.11

T;D

Sift4G

Uncertain

0.0040

D;T

Polyphen

0.0

.;B

Vest4

0.13

MutPred

0.41

.;Gain of catalytic residue at L81 (P = 0.0012);

MVP

0.67

MPC

0.28

ClinPred

0.20

GERP RS

2.5

Varity_R

0.10

gMVP

0.50

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr14-105478788-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over