rs10318

Variant names:

• chr15-32733778-C-T
• rs10318
• NM_013372.7:c.*2533C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013372.7(GREM1):​c.*2533C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 235,228 control chromosomes in the GnomAD database, including 5,363 homozygotes. 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 0.16 (2775 hom., cov: 33)
  • Exomes 𝑓: 0.22 (2588 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 35 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 Gene-Disease associations (from GenCC):

• hereditary mixed polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet
• polyposis syndrome, hereditary mixed, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013372.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM1	NM_013372.7	MANE Select	c.*2533C>T		3_prime_UTR	Exon 2 of 2	NP_037504.1	A6XAA7
	GREM1	NM_001368719.1		c.*2533C>T		3_prime_UTR	Exon 2 of 2	NP_001355648.1	O60565-1
	GREM1	NM_001191323.2		c.*2533C>T		3_prime_UTR	Exon 3 of 3	NP_001178252.1	O60565-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM1	ENST00000651154.1	MANE Select	c.*2533C>T		3_prime_UTR	Exon 2 of 2	ENSP00000498748.1	O60565-1
	GREM1	ENST00000652365.1		c.*2533C>T		3_prime_UTR	Exon 2 of 2	ENSP00000498763.1	O60565-1
	GREM1	ENST00000908783.1		c.*2533C>T		3_prime_UTR	Exon 2 of 2	ENSP00000578842.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24732 AN: 151802 Hom.: 2774 Cov.: 33

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.223 AC: 18593 AN: 83310 Hom.: 2588 Cov.: 0 AF XY: 0.224 AC XY: 8652 AN XY: 38576

African (AFR) AF: 0.0343 AC: 112 AN: 3268

American (AMR) AF: 0.173 AC: 359 AN: 2080

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 560 AN: 4382

East Asian (EAS) AF: 0.484 AC: 4669 AN: 9648

South Asian (SAS) AF: 0.277 AC: 167 AN: 602

European-Finnish (FIN) AF: 0.245 AC: 3609 AN: 14720

Middle Eastern (MID) AF: 0.162 AC: 68 AN: 420

European-Non Finnish (NFE) AF: 0.189 AC: 8003 AN: 42302

Other (OTH) AF: 0.178 AC: 1046 AN: 5888

GnomAD4 genome AF: 0.163 AC: 24732 AN: 151918 Hom.: 2775 Cov.: 33 AF XY: 0.169 AC XY: 12540 AN XY: 74236

African (AFR) AF: 0.0400 AC: 1659 AN: 41448

American (AMR) AF: 0.167 AC: 2552 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2737 AN: 5164

South Asian (SAS) AF: 0.288 AC: 1385 AN: 4810

European-Finnish (FIN) AF: 0.254 AC: 2675 AN: 10512

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12758 AN: 67932

Other (OTH) AF: 0.173 AC: 364 AN: 2106

Alfa AF: 0.180 Hom.: 8960

Bravo AF: 0.150

Asia WGS AF: 0.381 AC: 1321 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		2.7
Mutation Taster		=92/8	polymorphism (auto)

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: rs10318; hg19: chr15-33025979; COSMIC: COSV55714955; COSMIC: COSV55714955;