Variant 2-36356628-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_016441.3(CRIM1):c.331+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,602,680 control chromosomes in the GnomAD database, including 8 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 5 hom. )

Consequence

CRIM1
NM_016441.3 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.7414

Clinical Significance

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

Conservation

PhyloP100: 2.65

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 2-36356628-G-A is Benign according to our data. Variant chr2-36356628-G-A is described in ClinVar as [Benign]. Clinvar id is 777991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.331+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000280527.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CRIM1	ENST00000280527.7 linkuse as main transcript	c.331+5G>A	splice_donor_5th_base_variant, intron_variant	1	NM_016441.3	P1
CRIM1	ENST00000426856.1 linkuse as main transcript	c.181+5G>A	splice_donor_5th_base_variant, intron_variant	3
CRIM1	ENST00000428774.1 linkuse as main transcript	c.153+5G>A	splice_donor_5th_base_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

375

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00792

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000750

AC:

175

AN:

233474

Hom.:

AF XY:

0.000667

AC XY:

AN XY:

128872

show subpopulations

Gnomad AFR exome

AF:

0.00919

Gnomad AMR exome

AF:

0.000563

Gnomad ASJ exome

AF:

0.000422

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000337

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.000370

AC:

537

AN:

1450420

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

242

AN XY:

720912

show subpopulations

Gnomad4 AFR exome

AF:

0.00813

Gnomad4 AMR exome

AF:

0.000833

Gnomad4 ASJ exome

AF:

0.000737

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.0000207

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000750

GnomAD4 genome

AF:

0.00247

AC:

376

AN:

152260

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00789

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000927

Hom.:

Bravo

AF:

0.00312

Asia WGS

AF:

0.00173

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

Jul 13, 2018

- -

CRIM1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 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

-0.38

CADD

Benign

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.74

dbscSNV1_RF

Benign

0.52

SpliceAI score (max)

0.10

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