2-36356368-C-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_016441.3(CRIM1):c.76C>A(p.Leu26Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,595,650 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.00085 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 83 hom. )
Consequence
CRIM1
NM_016441.3 missense
NM_016441.3 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 0.755
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0062409043).
BP6
Variant 2-36356368-C-A is Benign according to our data. Variant chr2-36356368-C-A is described in ClinVar as [Benign]. Clinvar id is 3033563.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-36356368-C-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000847 (129/152246) while in subpopulation SAS AF= 0.0253 (122/4824). AF 95% confidence interval is 0.0216. There are 3 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRIM1 | NM_016441.3 | c.76C>A | p.Leu26Met | missense_variant | 1/17 | ENST00000280527.7 | NP_057525.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRIM1 | ENST00000280527.7 | c.76C>A | p.Leu26Met | missense_variant | 1/17 | 1 | NM_016441.3 | ENSP00000280527.2 |
Frequencies
GnomAD3 genomes AF: 0.000855 AC: 130AN: 152130Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00406 AC: 859AN: 211622Hom.: 30 AF XY: 0.00534 AC XY: 619AN XY: 116024
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GnomAD4 exome AF: 0.00185 AC: 2668AN: 1443404Hom.: 83 Cov.: 31 AF XY: 0.00264 AC XY: 1890AN XY: 716620
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GnomAD4 genome AF: 0.000847 AC: 129AN: 152246Hom.: 3 Cov.: 32 AF XY: 0.00122 AC XY: 91AN XY: 74424
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CRIM1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at