15-32720301-A-G

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+2140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,070 control chromosomes in the GnomAD database, including 5,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5281 hom., cov: 32)

Consequence

GREM1
NM_013372.7 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.0870
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 15-32720301-A-G is Benign according to our data. Variant chr15-32720301-A-G is described in ClinVar as [Benign]. Clinvar id is 1241475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GREM1NM_013372.7 linkuse as main transcriptc.-2+2140A>G intron_variant ENST00000651154.1
GREM1NM_001191322.2 linkuse as main transcriptc.-2+2140A>G intron_variant
GREM1NM_001191323.2 linkuse as main transcriptc.-2+2140A>G intron_variant
GREM1NM_001368719.1 linkuse as main transcriptc.-2+1599A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GREM1ENST00000651154.1 linkuse as main transcriptc.-2+2140A>G intron_variant NM_013372.7 P1O60565-1
GREM1ENST00000560677.5 linkuse as main transcriptc.-2+2140A>G intron_variant 4
GREM1ENST00000560830.1 linkuse as main transcriptc.-2+2140A>G intron_variant 2 O60565-2
GREM1ENST00000652365.1 linkuse as main transcriptc.-2+1599A>G intron_variant P1O60565-1

Frequencies

GnomAD3 genomes
AF:
0.251
AC:
38106
AN:
151952
Hom.:
5271
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.335
Gnomad AMI
AF:
0.0877
Gnomad AMR
AF:
0.194
Gnomad ASJ
AF:
0.142
Gnomad EAS
AF:
0.490
Gnomad SAS
AF:
0.312
Gnomad FIN
AF:
0.261
Gnomad MID
AF:
0.212
Gnomad NFE
AF:
0.197
Gnomad OTH
AF:
0.233
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.251
AC:
38149
AN:
152070
Hom.:
5281
Cov.:
32
AF XY:
0.254
AC XY:
18853
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.335
Gnomad4 AMR
AF:
0.194
Gnomad4 ASJ
AF:
0.142
Gnomad4 EAS
AF:
0.488
Gnomad4 SAS
AF:
0.313
Gnomad4 FIN
AF:
0.261
Gnomad4 NFE
AF:
0.197
Gnomad4 OTH
AF:
0.235
Alfa
AF:
0.211
Hom.:
824
Bravo
AF:
0.250
Asia WGS
AF:
0.410
AC:
1424
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Familial colorectal cancer Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 20, 2022- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
2.8
DANN
Benign
0.42

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.

Other links and lift over

dbSNP: rs73376930; hg19: chr15-33012502; API