Variant 2-36356318-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016441.3(CRIM1):c.26G>T(p.Gly9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,571,398 control chromosomes in the GnomAD database, including 1,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 158 hom., cov: 32)

Exomes 𝑓: 0.019 ( 1587 hom. )

Consequence

CRIM1
NM_016441.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.05

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]

CRIM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011918247).

BP6

Variant 2-36356318-G-T is Benign according to our data. Variant chr2-36356318-G-T is described in ClinVar as [Benign]. Clinvar id is 3059689.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRIM1	NM_016441.3 linkuse as main transcript	c.26G>T	p.Gly9Val	missense_variant	1/17	ENST00000280527.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRIM1	ENST00000280527.7 linkuse as main transcript	c.26G>T	p.Gly9Val	missense_variant	1/17	1	NM_016441.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2738

AN:

151966

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.00551

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.00751

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.00709

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00915

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0359

AC:

6631

AN:

184938

Hom.:

466

AF XY:

0.0353

AC XY:

3576

AN XY:

101226

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.0328

Gnomad ASJ exome

AF:

0.00592

Gnomad EAS exome

AF:

0.243

Gnomad SAS exome

AF:

0.0449

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.00980

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0190

AC:

26907

AN:

1419314

Hom.:

1587

Cov.:

AF XY:

0.0197

AC XY:

13850

AN XY:

702524

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.0308

Gnomad4 ASJ exome

AF:

0.00553

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.0465

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.00884

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.0180

AC:

2739

AN:

152084

Hom.:

158

Cov.:

AF XY:

0.0196

AC XY:

1459

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00296

Gnomad4 AMR

AF:

0.0216

Gnomad4 ASJ

AF:

0.00751

Gnomad4 EAS

AF:

0.249

Gnomad4 SAS

AF:

0.0493

Gnomad4 FIN

AF:

0.00709

Gnomad4 NFE

AF:

0.00915

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.0187

ESP6500AA

AF:

0.00125

AC:

ESP6500EA

AF:

0.00633

AC:

ExAC

AF:

0.0297

AC:

3478

Asia WGS

AF:

0.129

AC:

448

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CRIM1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.00087

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.22

REVEL

Benign

0.082

Sift

Uncertain

0.018

Sift4G

Pathogenic

0.0

Polyphen

0.0060

Vest4

0.19

MPC

0.97

ClinPred

0.025

GERP RS

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.10

gMVP

0.33

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