ENST00000558441.1:n.1041G>C

Variant names:

• chr15-32717967-C-G
• rs551795873
• ENST00000558441.1:n.1041G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The ENST00000558441.1(GREM1-AS1):​n.1041G>C 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 0.000637 in 1,051,416 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: GREM1-AS1 ENST00000558441.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.791
• Publications: 0 publications found

Genes affected

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

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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 15-32717967-C-G is Benign according to our data. Variant chr15-32717967-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2576286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-196C>G		upstream_gene_variant		ENST00000651154.1	NP_037504.1
GREM1	NM_001191323.2	c.-196C>G		upstream_gene_variant			NP_001178252.1
GREM1	NM_001191322.2	c.-196C>G		upstream_gene_variant			NP_001178251.1
GREM1-AS1	NR_109767.1	n.*134G>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-196C>G		upstream_gene_variant			NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-196C>G		upstream_gene_variant		4		ENSP00000453387.1

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 377 AN: 151798 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000318 AC: 286 AN: 899510 Hom.: 2 Cov.: 25 AF XY: 0.000342 AC XY: 142 AN XY: 415732

African (AFR) AF: 0.0110 AC: 205 AN: 18632

American (AMR) AF: 0.00107 AC: 3 AN: 2794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9096

East Asian (EAS) AF: 0.00 AC: 0 AN: 13204

South Asian (SAS) AF: 0.00 AC: 0 AN: 17762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2018

European-Non Finnish (NFE) AF: 0.0000449 AC: 36 AN: 802588

Other (OTH) AF: 0.00128 AC: 42 AN: 32790

GnomAD4 genome AF: 0.00253 AC: 384 AN: 151906 Hom.: 4 Cov.: 31 AF XY: 0.00273 AC XY: 203 AN XY: 74248

African (AFR) AF: 0.00878 AC: 364 AN: 41456

American (AMR) AF: 0.000654 AC: 10 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5062

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67940

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000278 Hom.: 0

Asia WGS AF: 0.00203 AC: 7 AN: 3460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		-0.79
PromoterAI		0.10	Neutral

Splicing

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

Other links and lift over

dbSNP: rs551795873; hg19: chr15-33010168;