15-32718122-C-T

Variant names:

• chr15-32718122-C-T
• rs1008800909
• NM_013372.7:c.-41C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_013372.7(GREM1):​c.-41C>T variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GREM1 NM_013372.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 15-32718122-C-T is Benign according to our data. Variant chr15-32718122-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3765305.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-41C>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000651154.1	NP_037504.1
GREM1-AS1	NR_109767.1	n.564G>A		non_coding_transcript_exon_variant	Exon 2 of 2
GREM1	NM_001191323.2	c.-41C>T		5_prime_UTR_variant	Exon 1 of 3		NP_001178252.1
GREM1	NM_001191322.2	c.-41C>T		5_prime_UTR_variant	Exon 1 of 3		NP_001178251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-41C>T		5_prime_UTR_variant	Exon 1 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-41C>T		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000453387.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1128134 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 541160

African (AFR) AF: 0.00 AC: 0 AN: 25104

American (AMR) AF: 0.00 AC: 0 AN: 20086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15250

East Asian (EAS) AF: 0.00 AC: 0 AN: 22494

South Asian (SAS) AF: 0.00 AC: 0 AN: 64620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 923076

Other (OTH) AF: 0.00 AC: 0 AN: 43852

GnomAD4 genome Cov.: 31

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	-0.50
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		0.055
PromoterAI		-0.17	Neutral
Mutation Taster		=277/23	polymorphism

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

Other links and lift over

dbSNP: rs1008800909; hg19: chr15-33010323;