dbSNP rs1555436514: CRIP2:p.Pro85Gln (chr14-105478788-C-A) – 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>A(p.Pro85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000781 in 1,281,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.0706673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIP2	NM_001312.4 link	c.254C>A	p.Pro85Gln	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>A	p.Pro85Gln	missense_variant	Exon 4 of 8	1	NM_001312.4	ENSP00000328521.5		P52943-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000211

AC:

AN:

47474

AF XY:

0.0000406

show subpopulations

Gnomad AFR exome

AF:

0.000296

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.81e-7

AC:

AN:

1281024

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

622978

show subpopulations

African (AFR)

AF:

0.0000376

AC:

AN:

26582

American (AMR)

AF:

0.00

AC:

AN:

19144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18640

East Asian (EAS)

AF:

0.00

AC:

AN:

33472

South Asian (SAS)

AF:

0.00

AC:

AN:

62512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3586

European-Non Finnish (NFE)

AF:

0.00

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.254C>A (p.P85Q) alteration is located in exon 4 (coding exon 4) of the CRIP2 gene. This alteration results from a C to A substitution at nucleotide position 254, causing the proline (P) at amino acid position 85 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

0.064

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.089

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

.;L

PhyloP100

0.10

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.1

D;N

REVEL

Benign

0.082

Sift

Benign

0.042

D;T

Sift4G

Uncertain

0.041

D;T

Polyphen

0.0

.;B

Vest4

0.10

MutPred

0.38

.;Gain of catalytic residue at L81 (P = 0.001);

MVP

0.56

MPC

0.23

ClinPred

0.093

GERP RS

2.5

Varity_R

0.098

gMVP

0.50

Mutation Taster

=92/8

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

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rs1555436514

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over