Variant 2-36356616-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_016441.3(CRIM1):c.324T>C(p.Val108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,606,594 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 4 hom. )

Consequence

CRIM1
NM_016441.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.418

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 2-36356616-T-C is Benign according to our data. Variant chr2-36356616-T-C is described in ClinVar as [Benign]. Clinvar id is 708457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.418 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRIM1	NM_016441.3 linkuse as main transcript	c.324T>C	p.Val108=	synonymous_variant	1/17	ENST00000280527.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CRIM1	ENST00000280527.7 linkuse as main transcript	c.324T>C	p.Val108=	synonymous_variant	1/17	1	NM_016441.3	P1
CRIM1	ENST00000426856.1 linkuse as main transcript	c.174T>C	p.Val58=	synonymous_variant	1/4	3
CRIM1	ENST00000428774.1 linkuse as main transcript	c.147T>C	p.Val49=	synonymous_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

389

AN:

151616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.00438

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00131

AC:

315

AN:

240974

Hom.:

AF XY:

0.00123

AC XY:

162

AN XY:

132124

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.000647

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000443

Gnomad SAS exome

AF:

0.00380

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000920

Gnomad OTH exome

AF:

0.000680

GnomAD4 exome

AF:

0.000458

AC:

667

AN:

1454860

Hom.:

Cov.:

AF XY:

0.000506

AC XY:

366

AN XY:

723552

show subpopulations

Gnomad4 AFR exome

AF:

0.00833

Gnomad4 AMR exome

AF:

0.000742

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000304

Gnomad4 SAS exome

AF:

0.00327

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000947

GnomAD4 genome

AF:

0.00256

AC:

388

AN:

151734

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.00844

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.00418

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00317

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

CRIM1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 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

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.74

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