Variant 2-36546976-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016441.3(CRIM1):c.2747-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000585 in 1,531,178 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00060 ( 2 hom. )

Consequence

CRIM1
NM_016441.3 splice_region, intron

Scores

Splicing: ADA: 0.00002543

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0930

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:

FEZ2 (HGNC:):

FEZ2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-36546976-T-C is Benign according to our data. Variant chr2-36546976-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3053471.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIM1	NM_016441.3 linkuse as main transcript	c.2747-8T>C		splice_region_variant, intron_variant		ENST00000280527.7	NP_057525.1	Q9NZV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIM1	ENST00000280527.7 linkuse as main transcript	c.2747-8T>C		splice_region_variant, intron_variant		1	NM_016441.3	ENSP00000280527.2		Q9NZV1
FEZ2	ENST00000406220.1 linkuse as main transcript	n.213+5080A>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000441

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000577

AC:

122

AN:

211538

Hom.:

AF XY:

0.000581

AC XY:

AN XY:

115316

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.0000889

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000978

Gnomad NFE exome

AF:

0.000959

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000600

AC:

828

AN:

1378996

Hom.:

Cov.:

AF XY:

0.000584

AC XY:

402

AN XY:

688194

show subpopulations

Gnomad4 AFR exome

AF:

0.000101

Gnomad4 AMR exome

AF:

0.0000302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.000707

Gnomad4 OTH exome

AF:

0.000262

GnomAD4 genome

AF:

0.000440

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000629

Hom.:

Bravo

AF:

0.000317

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

CRIM1: BP4 -

CRIM1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 13, 2020

This variant is classified as likely 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

-0.84

CADD

Benign

4.4

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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