NM_013372.7:c.*1009T>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 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.*1009T>G		3_prime_UTR	Exon 2 of 2	NP_037504.1	A6XAA7
	GREM1	NM_001368719.1		c.*1009T>G		3_prime_UTR	Exon 2 of 2	NP_001355648.1	O60565-1
	GREM1	NM_001191323.2		c.*1009T>G		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.*1009T>G		3_prime_UTR	Exon 2 of 2	ENSP00000498748.1	O60565-1
	GREM1	ENST00000652365.1		c.*1009T>G		3_prime_UTR	Exon 2 of 2	ENSP00000498763.1	O60565-1
	GREM1	ENST00000908783.1		c.*1009T>G		3_prime_UTR	Exon 2 of 2	ENSP00000578842.1

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

African (AFR) AF: 0.378 AC: 1278 AN: 3380

American (AMR) AF: 0.367 AC: 789 AN: 2152

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1489 AN: 4516

East Asian (EAS) AF: 0.323 AC: 3267 AN: 10130

South Asian (SAS) AF: 0.368 AC: 231 AN: 628

European-Finnish (FIN) AF: 0.287 AC: 4085 AN: 14220

Middle Eastern (MID) AF: 0.313 AC: 135 AN: 432

European-Non Finnish (NFE) AF: 0.278 AC: 12118 AN: 43550

Other (OTH) AF: 0.296 AC: 1778 AN: 6004

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

African (AFR) AF: 0.380 AC: 15750 AN: 41440

American (AMR) AF: 0.356 AC: 5440 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1149 AN: 5156

South Asian (SAS) AF: 0.352 AC: 1687 AN: 4798

European-Finnish (FIN) AF: 0.286 AC: 3014 AN: 10544

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19608 AN: 67956

Other (OTH) AF: 0.305 AC: 643 AN: 2110

Alfa AF: 0.300 Hom.: 27629

Bravo AF: 0.328

Asia WGS AF: 0.317 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.54
PhyloP100		0.43
Mutation Taster		=100/0	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: rs7162202; hg19: chr15-33024455; COSMIC: COSV55716210; COSMIC: COSV55716210;