Variant chr15-32733778-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013372.7(GREM1):c.*2533C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 235,228 control chromosomes in the GnomAD database, including 5,363 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 0.16 ( 2775 hom., cov: 33)

Exomes 𝑓: 0.22 ( 2588 hom. )

Consequence

GREM1
NM_013372.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
GREM1	NM_013372.7 linkuse as main transcript	c.*2533C>T	3_prime_UTR_variant	2/2	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001368719.1 linkuse as main transcript	c.*2533C>T	3_prime_UTR_variant	2/2		NP_001355648.1
GREM1	NM_001191323.2 linkuse as main transcript	c.*2533C>T	3_prime_UTR_variant	3/3		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 linkuse as main transcript	c.*2533C>T	3_prime_UTR_variant	3/3		NP_001178251.1	B3KTR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1 linkuse as main transcript	c.*2533C>T		3_prime_UTR_variant	2/2		NM_013372.7	ENSP00000498748.1		O60565-1
GREM1	ENST00000652365.1 linkuse as main transcript	c.*2533C>T		3_prime_UTR_variant	2/2			ENSP00000498763.1		O60565-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24732

AN:

151802

Hom.:

2774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.168

GnomAD4 exome

AF:

0.223

AC:

18593

AN:

83310

Hom.:

2588

Cov.:

AF XY:

0.224

AC XY:

8652

AN XY:

38576

show subpopulations

Gnomad4 AFR exome

AF:

0.0343

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.163

AC:

24732

AN:

151918

Hom.:

2775

Cov.:

AF XY:

0.169

AC XY:

12540

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.530

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.181

Hom.:

4059

Bravo

AF:

0.150

Asia WGS

AF:

0.381

AC:

1321

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over