Variant 15-32718282-T-C details in Genebe, Genetics Data Aggregator

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+121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 739,950 control chromosomes in the GnomAD database, including 2,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 415 hom., cov: 32)

Exomes 𝑓: 0.082 ( 2314 hom. )

Consequence

GREM1
NM_013372.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0880

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:

GREM1-AS1 (HGNC:55411): (GREM1 antisense RNA 1)

GREM1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-32718282-T-C is Benign according to our data. Variant chr15-32718282-T-C is described in ClinVar as [Benign]. Clinvar id is 1247744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GREM1	NM_013372.7 linkuse as main transcript	c.-2+121T>C	intron_variant		ENST00000651154.1
GREM1-AS1	NR_109767.1 linkuse as main transcript	n.404A>G	non_coding_transcript_exon_variant	2/2
GREM1	NM_001191322.2 linkuse as main transcript	c.-2+121T>C	intron_variant
GREM1	NM_001191323.2 linkuse as main transcript	c.-2+121T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREM1	ENST00000651154.1 linkuse as main transcript	c.-2+121T>C		intron_variant			NM_013372.7	P1	O60565-1
GREM1-AS1	ENST00000558441.1 linkuse as main transcript	n.726A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0651

AC:

9898

AN:

152062

Hom.:

415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.0681

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.0875

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0986

Gnomad OTH

AF:

0.0770

GnomAD3 exomes

AF:

0.0621

AC:

8316

AN:

133822

Hom.:

356

AF XY:

0.0612

AC XY:

4467

AN XY:

72998

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.0517

Gnomad ASJ exome

AF:

0.0486

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0230

Gnomad FIN exome

AF:

0.0841

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.0795

GnomAD4 exome

AF:

0.0818

AC:

48101

AN:

587776

Hom.:

2314

Cov.:

AF XY:

0.0787

AC XY:

24192

AN XY:

307348

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.0523

Gnomad4 ASJ exome

AF:

0.0485

Gnomad4 EAS exome

AF:

0.000258

Gnomad4 SAS exome

AF:

0.0205

Gnomad4 FIN exome

AF:

0.0836

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.0799

GnomAD4 genome

AF:

0.0651

AC:

9900

AN:

152174

Hom.:

415

Cov.:

AF XY:

0.0631

AC XY:

4698

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.0680

Gnomad4 ASJ

AF:

0.0478

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.0875

Gnomad4 NFE

AF:

0.0986

Gnomad4 OTH

AF:

0.0762

Alfa

AF:

0.0835

Hom.:

177

Bravo

AF:

0.0627

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.2

DANN

Benign

0.23

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over