14-105478818-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001312.4(CRIP2):​c.284C>T​(p.Ala95Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,430,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000070 ( 1 hom. )

Consequence

CRIP2
NM_001312.4 missense

Scores

1
1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06811389).
BP6
Variant 14-105478818-C-T is Benign according to our data. Variant chr14-105478818-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3497084.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRIP2NM_001312.4 linkc.284C>T p.Ala95Val 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
CRIP2ENST00000329146.9 linkc.284C>T p.Ala95Val missense_variant Exon 4 of 8 1 NM_001312.4 ENSP00000328521.5 P52943-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151858
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000232
AC:
1
AN:
43110
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
22766
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000112
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000704
AC:
9
AN:
1278518
Hom.:
1
Cov.:
38
AF XY:
0.00000964
AC XY:
6
AN XY:
622594
show subpopulations
Gnomad4 AFR exome
AF:
0.000156
Gnomad4 AMR exome
AF:
0.0000543
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000161
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000194
Gnomad4 OTH exome
AF:
0.0000189
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151858
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74164
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Nov 08, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
1.9
DANN
Benign
0.96
DEOGEN2
Benign
0.058
.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.54
T;T
M_CAP
Pathogenic
0.37
D
MetaRNN
Benign
0.068
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.41
.;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.050
N;N
REVEL
Benign
0.072
Sift
Benign
0.29
T;T
Sift4G
Benign
0.47
T;T
Polyphen
0.0010
.;B
Vest4
0.090
MutPred
0.49
.;Gain of relative solvent accessibility (P = 0.0483);
MVP
0.43
MPC
0.24
ClinPred
0.036
T
GERP RS
-2.0
Varity_R
0.023
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1301487932; hg19: chr14-105945155; API