GeneBe

rs12324639

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000908783.1(GREM1):​c.-2+781G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GREM1
ENST00000908783.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

Publications

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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908783.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GREM1
NM_013372.7
MANE Select
c.-272G>A
upstream_gene
N/ANP_037504.1A6XAA7
GREM1
NM_001191323.2
c.-272G>A
upstream_gene
N/ANP_001178252.1O60565-2
GREM1
NM_001191322.2
c.-272G>A
upstream_gene
N/ANP_001178251.1B3KTR9

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GREM1
ENST00000908783.1
c.-2+781G>A
intron
N/AENSP00000578842.1
GREM1-AS1
ENST00000558441.1
TSL:6
n.1117C>T
non_coding_transcript_exon
Exon 1 of 1
GREM1
ENST00000651154.1
MANE Select
c.-272G>A
upstream_gene
N/AENSP00000498748.1O60565-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
287086
Hom.:
0
Cov.:
5
AF XY:
0.00
AC XY:
0
AN XY:
135824
African (AFR)
AF:
0.00
AC:
0
AN:
6450
American (AMR)
AF:
0.00
AC:
0
AN:
1576
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
4332
East Asian (EAS)
AF:
0.00
AC:
0
AN:
8328
South Asian (SAS)
AF:
0.00
AC:
0
AN:
5374
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
164
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
770
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
248420
Other (OTH)
AF:
0.00
AC:
0
AN:
11672
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
20
DANN
Benign
0.97
PhyloP100
2.1
PromoterAI
-0.047
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs12324639; hg19: chr15-33010092; API