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GeneBe

2-36441366-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016441.3(CRIM1):ā€‹c.614C>Gā€‹(p.Pro205Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,614,060 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000027 ( 1 hom. )

Consequence

CRIM1
NM_016441.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98
Variant links:
Genes affected
CRIM1 (HGNC:2359): (cysteine rich transmembrane BMP regulator 1) This gene encodes a transmembrane protein containing six cysteine-rich repeat domains and an insulin-like growth factor-binding domain. The encoded protein may play a role in tissue development though interactions with members of the transforming growth factor beta family, such as bone morphogenetic proteins. [provided by RefSeq, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRIM1NM_016441.3 linkuse as main transcriptc.614C>G p.Pro205Arg missense_variant 3/17 ENST00000280527.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRIM1ENST00000280527.7 linkuse as main transcriptc.614C>G p.Pro205Arg missense_variant 3/171 NM_016441.3 P1
CRIM1ENST00000426856.1 linkuse as main transcriptc.290C>G p.Pro97Arg missense_variant 2/43

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152184
Hom.:
0
Cov.:
32
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:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251206
Hom.:
1
AF XY:
0.0000295
AC XY:
4
AN XY:
135764
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461876
Hom.:
1
Cov.:
32
AF XY:
0.0000330
AC XY:
24
AN XY:
727240
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:
0.0000342
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74350
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:
0.0000441
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000501
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsAug 08, 2023The c.614C>G (p.P205R) alteration is located in exon 3 (coding exon 3) of the CRIM1 gene. This alteration results from a C to G substitution at nucleotide position 614, causing the proline (P) at amino acid position 205 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
Pathogenic
0.86
BayesDel_addAF
Benign
-0.0098
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.9
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.9
D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0050
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.87
MutPred
0.47
Loss of glycosylation at S208 (P = 0.0823);.;
MVP
0.29
MPC
0.89
ClinPred
0.87
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.50
gMVP
0.69

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.

Other links and lift over

dbSNP: rs771686787; hg19: chr2-36668509; API