Variant rs1129456 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.*3221A>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 0.165 in 246,262 control chromosomes in the GnomAD database, including 4,520 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 0.18 ( 3512 hom., cov: 33)

Exomes 𝑓: 0.13 ( 1008 hom. )

Consequence

GREM1
NM_013372.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.385

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=-0.62).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
GREM1	NM_013372.7 link	c.*3221A>T	3_prime_UTR_variant	2/2	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001368719.1 link	c.*3221A>T	3_prime_UTR_variant	2/2		NP_001355648.1
GREM1	NM_001191323.2 link	c.*3221A>T	3_prime_UTR_variant	3/3		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 link	c.*3221A>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 link	c.*3221A>T		3_prime_UTR_variant	2/2		NM_013372.7	ENSP00000498748.1		O60565-1
GREM1	ENST00000652365.1 link	c.*3221A>T		3_prime_UTR_variant	2/2			ENSP00000498763.1		O60565-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28019

AN:

152080

Hom.:

3480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.134

AC:

12575

AN:

94064

Hom.:

1008

Cov.:

AF XY:

0.131

AC XY:

5723

AN XY:

43554

show subpopulations

Gnomad4 AFR exome

AF:

0.359

Gnomad4 AMR exome

AF:

0.0976

Gnomad4 ASJ exome

AF:

0.0988

Gnomad4 EAS exome

AF:

0.159

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.185

AC:

28106

AN:

152198

Hom.:

3512

Cov.:

AF XY:

0.184

AC XY:

13687

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.354

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0896

Gnomad4 EAS

AF:

0.210

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.155

Hom.:

304

Bravo

AF:

0.191

Asia WGS

AF:

0.174

AC:

606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.9

DANN

Benign

0.81

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