Variant 14-105478846-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001312.4(CRIP2):c.312C>A(p.Ser104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000772 in 1,425,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.978

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 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity CRIP2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23277554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIP2	NM_001312.4 linkuse as main transcript	c.312C>A	p.Ser104Arg	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.312C>A	p.Ser104Arg	missense_variant	4/8	1	NM_001312.4	ENSP00000328521	P1	P52943-1

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000157

AC:

AN:

1273786

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

620416

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:

0.00000194

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151808

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.000218

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000491

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 13, 2023

The c.312C>A (p.S104R) 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 312, causing the serine (S) at amino acid position 104 to be replaced by an arginine (R). 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

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.6

DANN

Uncertain

0.98

DEOGEN2

Benign

0.082

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.67

T;T

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.089

Sift

Benign

0.049

D;T

Sift4G

Benign

0.095

T;T

Polyphen

0.45

.;B

Vest4

0.11

MutPred

0.38

.;Gain of catalytic residue at P106 (P = 0.0016);

MVP

0.66

MPC

0.51

ClinPred

0.50

GERP RS

-2.1

Varity_R

0.067

gMVP

0.41

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