Genetic Variant GREM1-AS1:n.1054G>T (chr15-32717954-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000558441.1(GREM1-AS1):n.1054G>T 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 0.00000659 in 151,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GREM1-AS1
ENST00000558441.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.210

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GREM1	NM_013372.7 link	c.-209C>A	upstream_gene_variant	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001191323.2 link	c.-209C>A	upstream_gene_variant		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 link	c.-209C>A	upstream_gene_variant		NP_001178251.1	B3KTR9
GREM1-AS1	NR_109767.1 link	n.*147G>T	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1 link	c.-209C>A		upstream_gene_variant			NM_013372.7	ENSP00000498748.1		O60565-1
GREM1	ENST00000560677.5 link	c.-209C>A		upstream_gene_variant		4		ENSP00000453387.1		H0YLY2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151664

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

870574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

402814

African (AFR)

AF:

0.00

AC:

AN:

17940

American (AMR)

AF:

0.00

AC:

AN:

2688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8752

East Asian (EAS)

AF:

0.00

AC:

AN:

12668

South Asian (SAS)

AF:

0.00

AC:

AN:

17042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1946

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

777382

Other (OTH)

AF:

0.00

AC:

AN:

31604

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151664

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74094

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41318

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5054

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67878

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.21

PromoterAI

-0.034

Neutral

(source)

Splicing

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

Publications

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15-32717954-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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