Genetic Variant GREM1:c.*2181C>T (chr15-32733426-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_013372.7(GREM1):c.*2181C>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 0.518 in 228,252 control chromosomes in the GnomAD database, including 31,915 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 0.50 ( 19832 hom., cov: 33)

Exomes 𝑓: 0.56 ( 12083 hom. )

Consequence

GREM1
NM_013372.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.940

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=-0.66).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7 link	c.*2181C>T	3_prime_UTR_variant	Exon 2 of 2	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001368719.1 link	c.*2181C>T	3_prime_UTR_variant	Exon 2 of 2		NP_001355648.1
GREM1	NM_001191323.2 link	c.*2181C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 link	c.*2181C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001178251.1	B3KTR9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GREM1	ENST00000651154.1 link	c.*2181C>T	3_prime_UTR_variant	Exon 2 of 2		NM_013372.7	ENSP00000498748.1	O60565-1
GREM1	ENST00000652365.1 link	c.*2181C>T	3_prime_UTR_variant	Exon 2 of 2			ENSP00000498763.1	O60565-1
GREM1	ENST00000560830.1 link	c.*2181C>T	downstream_gene_variant		2		ENSP00000453141.1	O60565-2

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75669

AN:

151952

Hom.:

19825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.518

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.509

GnomAD4 exome

AF:

0.558

AC:

42496

AN:

76180

Hom.:

12083

Cov.:

AF XY:

0.564

AC XY:

19993

AN XY:

35444

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.566

Gnomad4 EAS exome

AF:

0.504

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.498

AC:

75707

AN:

152072

Hom.:

19832

Cov.:

AF XY:

0.501

AC XY:

37221

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.520

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.553

Gnomad4 SAS

AF:

0.520

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.580

Gnomad4 OTH

AF:

0.512

Alfa

AF:

0.555

Hom.:

25520

Bravo

AF:

0.485

Asia WGS

AF:

0.518

AC:

1805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.9

DANN

Benign

0.68

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