Variant 2-36441451-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016441.3(CRIM1):c.699A>G(p.Lys233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,613,800 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 46 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 37 hom. )

Consequence

CRIM1
NM_016441.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.435

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 2-36441451-A-G is Benign according to our data. Variant chr2-36441451-A-G is described in ClinVar as [Benign]. Clinvar id is 789559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.435 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1959/152362) while in subpopulation AFR AF= 0.0449 (1865/41580). AF 95% confidence interval is 0.0432. There are 46 homozygotes in gnomad4. There are 899 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRIM1	NM_016441.3 linkuse as main transcript	c.699A>G	p.Lys233=	synonymous_variant	3/17	ENST00000280527.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRIM1	ENST00000280527.7 linkuse as main transcript	c.699A>G	p.Lys233=	synonymous_variant	3/17	1	NM_016441.3	P1
CRIM1	ENST00000426856.1 linkuse as main transcript	c.375A>G	p.Lys125=	synonymous_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1954

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00314

AC:

787

AN:

250928

Hom.:

AF XY:

0.00212

AC XY:

287

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00134

AC:

1957

AN:

1461438

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

851

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0498

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.0129

AC:

1959

AN:

152362

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

899

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0449

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00574

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

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

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.9

DANN

Benign

0.62

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