rs534996132

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.755

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

colobomatous macrophthalmia-microcornea syndrome
Inheritance: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

CRIM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 129 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIM1	NM_016441.3 link	c.76C>A	p.Leu26Met	missense_variant	Exon 1 of 17	ENST00000280527.7	NP_057525.1	Q9NZV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRIM1	ENST00000280527.7 link	c.76C>A	p.Leu26Met	missense_variant	Exon 1 of 17	1	NM_016441.3	ENSP00000280527.2	Q9NZV1
CRIM1	ENST00000426856.1 link	c.-75C>A		upstream_gene_variant		3		ENSP00000407636.1	H7C2T6
CRIM1	ENST00000428774.1 link	c.-105C>A		upstream_gene_variant		3		ENSP00000415706.1	H7C458

Frequencies

GnomAD3 genomes

AF:

0.000855

AC:

130

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00406

AC:

859

AN:

211622

AF XY:

0.00534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.000124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000348

Gnomad OTH exome

AF:

0.00303

GnomAD4 exome

AF:

0.00185

AC:

2668

AN:

1443404

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

1890

AN XY:

716620

show subpopulations

African (AFR)

AF:

0.0000906

AC:

AN:

33114

American (AMR)

AF:

0.0000470

AC:

AN:

42538

Ashkenazi Jewish (ASJ)

AF:

0.0000390

AC:

AN:

25652

East Asian (EAS)

AF:

0.0000769

AC:

AN:

39022

South Asian (SAS)

AF:

0.0272

AC:

2285

AN:

84136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4440

European-Non Finnish (NFE)

AF:

0.000203

AC:

224

AN:

1105490

Other (OTH)

AF:

0.00252

AC:

150

AN:

59528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

134

267

401

534

668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000847

AC:

129

AN:

152246

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41570

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.0253

AC:

122

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67990

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000224

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.00408

AC:

485

Asia WGS

AF:

0.00898

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CRIM1-related disorder

Benign:1

Jul 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.17

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

0.76

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.10

REVEL

Benign

0.031

Sift

Benign

0.16

Sift4G

Uncertain

0.046

Polyphen

0.12

Vest4

0.45

MVP

0.13

MPC

0.78

ClinPred

0.038

GERP RS

1.4

PromoterAI

-0.16

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.12

gMVP

0.086

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs534996132

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over