15-32732254-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013372.7(GREM1):​c.*1009T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 236,964 control chromosomes in the GnomAD database, including 11,965 homozygotes. 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: 𝑓 0.32 ( 8149 hom., cov: 32)
Exomes 𝑓: 0.30 ( 3816 hom. )

Consequence

GREM1
NM_013372.7 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.434
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GREM1NM_013372.7 linkc.*1009T>G 3_prime_UTR_variant Exon 2 of 2 ENST00000651154.1 NP_037504.1 O60565-1A6XAA7
GREM1NM_001368719.1 linkc.*1009T>G 3_prime_UTR_variant Exon 2 of 2 NP_001355648.1
GREM1NM_001191323.2 linkc.*1009T>G 3_prime_UTR_variant Exon 3 of 3 NP_001178252.1 O60565-2
GREM1NM_001191322.2 linkc.*1009T>G 3_prime_UTR_variant Exon 3 of 3 NP_001178251.1 B3KTR9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GREM1ENST00000651154.1 linkc.*1009T>G 3_prime_UTR_variant Exon 2 of 2 NM_013372.7 ENSP00000498748.1 O60565-1
GREM1ENST00000652365.1 linkc.*1009T>G 3_prime_UTR_variant Exon 2 of 2 ENSP00000498763.1 O60565-1
GREM1ENST00000560830.1 linkc.*1009T>G 3_prime_UTR_variant Exon 3 of 3 2 ENSP00000453141.1 O60565-2

Frequencies

GnomAD3 genomes
AF:
0.322
AC:
48909
AN:
151834
Hom.:
8145
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.380
Gnomad AMI
AF:
0.492
Gnomad AMR
AF:
0.356
Gnomad ASJ
AF:
0.322
Gnomad EAS
AF:
0.222
Gnomad SAS
AF:
0.354
Gnomad FIN
AF:
0.286
Gnomad MID
AF:
0.301
Gnomad NFE
AF:
0.289
Gnomad OTH
AF:
0.308
GnomAD4 exome
AF:
0.296
AC:
25170
AN:
85012
Hom.:
3816
Cov.:
0
AF XY:
0.293
AC XY:
11566
AN XY:
39488
show subpopulations
Gnomad4 AFR exome
AF:
0.378
Gnomad4 AMR exome
AF:
0.367
Gnomad4 ASJ exome
AF:
0.330
Gnomad4 EAS exome
AF:
0.323
Gnomad4 SAS exome
AF:
0.368
Gnomad4 FIN exome
AF:
0.287
Gnomad4 NFE exome
AF:
0.278
Gnomad4 OTH exome
AF:
0.296
GnomAD4 genome
AF:
0.322
AC:
48945
AN:
151952
Hom.:
8149
Cov.:
32
AF XY:
0.321
AC XY:
23811
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.380
Gnomad4 AMR
AF:
0.356
Gnomad4 ASJ
AF:
0.322
Gnomad4 EAS
AF:
0.223
Gnomad4 SAS
AF:
0.352
Gnomad4 FIN
AF:
0.286
Gnomad4 NFE
AF:
0.289
Gnomad4 OTH
AF:
0.305
Alfa
AF:
0.287
Hom.:
10700
Bravo
AF:
0.328
Asia WGS
AF:
0.317
AC:
1098
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.5
DANN
Benign
0.54

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: rs7162202; hg19: chr15-33024455; COSMIC: COSV55716210; COSMIC: COSV55716210; API