rs12324639

Variant names:

• chr15-32717891-G-A
• rs12324639
• ENST00000558441.1:n.1117C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-32717891-G-A
• chr15-32717891-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000558441.1(GREM1-AS1):​n.1117C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GREM1-AS1 ENST00000558441.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 1 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: 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=-0.33).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-272G>A		upstream_gene_variant		ENST00000651154.1	NP_037504.1
GREM1	NM_001191323.2	c.-272G>A		upstream_gene_variant			NP_001178252.1
GREM1	NM_001191322.2	c.-272G>A		upstream_gene_variant			NP_001178251.1
GREM1-AS1	NR_109767.1	n.*210C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-272G>A		upstream_gene_variant			NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-272G>A		upstream_gene_variant		4		ENSP00000453387.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 287086 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 135824

African (AFR) AF: 0.00 AC: 0 AN: 6450

American (AMR) AF: 0.00 AC: 0 AN: 1576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4332

East Asian (EAS) AF: 0.00 AC: 0 AN: 8328

South Asian (SAS) AF: 0.00 AC: 0 AN: 5374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 248420

Other (OTH) AF: 0.00 AC: 0 AN: 11672

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		2.1
PromoterAI		-0.047	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12324639; hg19: chr15-33010092;