15-32732254-T-G

Variant names:

• chr15-32732254-T-G
• rs7162202
• NM_013372.7:c.*1009T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013372.7(GREM1):​c.*1009T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 236,964 control chromosomes in the GnomAD database, including 11,965 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 0.32 (8149 hom., cov: 32)
  • Exomes 𝑓: 0.30 (3816 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.*1009T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000651154.1	NP_037504.1
GREM1	NM_001368719.1	c.*1009T>G		3_prime_UTR_variant	Exon 2 of 2		NP_001355648.1
GREM1	NM_001191323.2	c.*1009T>G		3_prime_UTR_variant	Exon 3 of 3		NP_001178252.1
GREM1	NM_001191322.2	c.*1009T>G		3_prime_UTR_variant	Exon 3 of 3		NP_001178251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.*1009T>G		3_prime_UTR_variant	Exon 2 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000652365.1	c.*1009T>G		3_prime_UTR_variant	Exon 2 of 2			ENSP00000498763.1
GREM1	ENST00000560830.1	c.*1009T>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000453141.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48909 AN: 151834 Hom.: 8145 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.296 AC: 25170 AN: 85012 Hom.: 3816 Cov.: 0 AF XY: 0.293 AC XY: 11566 AN XY: 39488

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.322 AC: 48945 AN: 151952 Hom.: 8149 Cov.: 32 AF XY: 0.321 AC XY: 23811 AN XY: 74254

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.305

Alfa AF: 0.287 Hom.: 10700

Bravo AF: 0.328

Asia WGS AF: 0.317 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.54

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: rs7162202; hg19: chr15-33024455; COSMIC: COSV55716210; COSMIC: COSV55716210;