Variant 15-32718211-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013372.7(GREM1):c.-2+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,306,870 control chromosomes in the GnomAD database, including 29,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3428 hom., cov: 31)

Exomes 𝑓: 0.21 ( 26462 hom. )

Consequence

GREM1
NM_013372.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.45

Variant links:

Genes affected

GREM1 (HGNC:2001): (gremlin 1, DAN family BMP antagonist) This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

GREM1 links:

GREM1-AS1 (HGNC:55411): (GREM1 antisense RNA 1)

GREM1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-32718211-G-A is Benign according to our data. Variant chr15-32718211-G-A is described in ClinVar as [Benign]. Clinvar id is 1297801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7 link	c.-2+50G>A	intron_variant	Intron 1 of 1	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001191323.2 link	c.-2+50G>A	intron_variant	Intron 1 of 2		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 link	c.-2+50G>A	intron_variant	Intron 1 of 2		NP_001178251.1	B3KTR9
GREM1-AS1	NR_109767.1 link	n.475C>T	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1 link	c.-2+50G>A		intron_variant	Intron 1 of 1		NM_013372.7	ENSP00000498748.1		O60565-1
GREM1	ENST00000560677.5 link	c.-2+50G>A		intron_variant	Intron 1 of 2	4		ENSP00000453387.1		H0YLY2

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30825

AN:

151870

Hom.:

3425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.231

AC:

30164

AN:

130592

Hom.:

4086

AF XY:

0.235

AC XY:

16755

AN XY:

71148

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.491

Gnomad SAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.207

AC:

238736

AN:

1154882

Hom.:

26462

Cov.:

AF XY:

0.209

AC XY:

117973

AN XY:

564472

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.483

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.203

AC:

30839

AN:

151988

Hom.:

3428

Cov.:

AF XY:

0.207

AC XY:

15356

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.481

Gnomad4 SAS

AF:

0.303

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.191

Hom.:

560

Bravo

AF:

0.195

Asia WGS

AF:

0.397

AC:

1378

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27379672) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

DANN

Benign

0.86

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