rs556187651

Variant names:

• chr15-32718052-G-A
• rs556187651
• NM_013372.7:c.-111G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013372.7(GREM1):​c.-111G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,168,238 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (7 hom., cov: 31)
  • Exomes 𝑓: 0.00067 (3 hom.)
• Consequence: GREM1 NM_013372.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 15-32718052-G-A is Benign according to our data. Variant chr15-32718052-G-A is described in ClinVar as [Benign]. Clinvar id is 1697735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 634 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-111G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000651154.1	NP_037504.1
GREM1	NM_001191323.2	c.-111G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001178252.1
GREM1	NM_001191322.2	c.-111G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001178251.1
GREM1-AS1	NR_109767.1	n.*49C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-111G>A		5_prime_UTR_variant	Exon 1 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-111G>A		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000453387.1

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 624 AN: 151950 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00108 AC: 9 AN: 8366 AF XY: 0.00159

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000720

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000671 AC: 682 AN: 1016180 Hom.: 3 Cov.: 30 AF XY: 0.000598 AC XY: 287 AN XY: 479922

African (AFR) AF: 0.0159 AC: 313 AN: 19634

American (AMR) AF: 0.00365 AC: 20 AN: 5478

Ashkenazi Jewish (ASJ) AF: 0.000341 AC: 4 AN: 11734

East Asian (EAS) AF: 0.00 AC: 0 AN: 16172

South Asian (SAS) AF: 0.0000703 AC: 3 AN: 42676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7342

Middle Eastern (MID) AF: 0.00481 AC: 12 AN: 2494

European-Non Finnish (NFE) AF: 0.000294 AC: 256 AN: 871798

Other (OTH) AF: 0.00190 AC: 74 AN: 38852

GnomAD4 genome AF: 0.00417 AC: 634 AN: 152058 Hom.: 7 Cov.: 31 AF XY: 0.00377 AC XY: 280 AN XY: 74354

African (AFR) AF: 0.0137 AC: 568 AN: 41510

American (AMR) AF: 0.00209 AC: 32 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67944

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00409 Hom.: 0

Bravo AF: 0.00479

Asia WGS AF: 0.00145 AC: 5 AN: 3456

ClinVar

Significance: 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: 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	-0.67
CADD	Benign	2.7
DANN	Benign	0.96
PhyloP100		-1.6
PromoterAI		-0.22	Neutral
Mutation Taster		=300/0	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: rs556187651; hg19: chr15-33010253;