rs10318

Positions:

• chr15-32733778-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREM1	NM_013372.7	c.*2533C>T		3_prime_UTR_variant	2/2	ENST00000651154.1	NP_037504.1
GREM1	NM_001368719.1	c.*2533C>T		3_prime_UTR_variant	2/2		NP_001355648.1
GREM1	NM_001191323.2	c.*2533C>T		3_prime_UTR_variant	3/3		NP_001178252.1
GREM1	NM_001191322.2	c.*2533C>T		3_prime_UTR_variant	3/3		NP_001178251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.*2533C>T		3_prime_UTR_variant	2/2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000652365.1	c.*2533C>T		3_prime_UTR_variant	2/2			ENSP00000498763.1

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

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.178

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

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.173

Alfa AF: 0.181 Hom.: 4059

Bravo AF: 0.150

Asia WGS AF: 0.381 AC: 1321 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

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