Genetic Variant ENST00000558441.1:n.1037C>A (chr15-32717971-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000558441.1(GREM1-AS1):n.1037C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,052,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

GREM1-AS1
ENST00000558441.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620

Publications

0 publications found

Variant links:

Genes affected

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

GREM1-AS1 links:

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 Gene-Disease associations (from GenCC):

hereditary mixed polyposis syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P
polyposis syndrome, hereditary mixed, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

GREM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 15-32717971-G-T is Benign according to our data. Variant chr15-32717971-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1802876.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GREM1	NM_013372.7 link	c.-192G>T	upstream_gene_variant	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001191323.2 link	c.-192G>T	upstream_gene_variant		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 link	c.-192G>T	upstream_gene_variant		NP_001178251.1	B3KTR9
GREM1-AS1	NR_109767.1 link	n.*130C>A	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1 link	c.-192G>T		upstream_gene_variant			NM_013372.7	ENSP00000498748.1		O60565-1
GREM1	ENST00000560677.5 link	c.-192G>T		upstream_gene_variant		4		ENSP00000453387.1		H0YLY2

Frequencies

GnomAD3 genomes

AF:

0.000303

AC:

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00369

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.0000799

AC:

AN:

901138

Hom.:

Cov.:

AF XY:

0.0000985

AC XY:

AN XY:

416434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18720

American (AMR)

AF:

0.00

AC:

AN:

2838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9160

East Asian (EAS)

AF:

0.00

AC:

AN:

13312

South Asian (SAS)

AF:

0.00

AC:

AN:

17768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2022

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

803850

Other (OTH)

AF:

0.0000304

AC:

AN:

32856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000303

AC:

AN:

151820

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41368

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5094

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00369

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67922

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.062

PromoterAI

-0.048

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000558441.1:n.1037C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over