NM_013372.7:c.*2181C>T

Variant names:

• chr15-32733426-C-T
• rs3743103
• NM_013372.7:c.*2181C>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.*2181C>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 0.518 in 228,252 control chromosomes in the GnomAD database, including 31,915 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 0.50 (19832 hom., cov: 33)
  • Exomes 𝑓: 0.56 (12083 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940
• Publications: 15 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 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.*2181C>T		3_prime_UTR	Exon 2 of 2	NP_037504.1	A6XAA7
	GREM1	NM_001368719.1		c.*2181C>T		3_prime_UTR	Exon 2 of 2	NP_001355648.1	O60565-1
	GREM1	NM_001191323.2		c.*2181C>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.*2181C>T		3_prime_UTR	Exon 2 of 2	ENSP00000498748.1	O60565-1
	GREM1	ENST00000652365.1		c.*2181C>T		3_prime_UTR	Exon 2 of 2	ENSP00000498763.1	O60565-1
	GREM1	ENST00000908783.1		c.*2181C>T		3_prime_UTR	Exon 2 of 2	ENSP00000578842.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75669 AN: 151952 Hom.: 19825 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.558 AC: 42496 AN: 76180 Hom.: 12083 Cov.: 0 AF XY: 0.564 AC XY: 19993 AN XY: 35444

African (AFR) AF: 0.304 AC: 855 AN: 2810

American (AMR) AF: 0.508 AC: 904 AN: 1778

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 2228 AN: 3934

East Asian (EAS) AF: 0.504 AC: 4646 AN: 9224

South Asian (SAS) AF: 0.500 AC: 266 AN: 532

European-Finnish (FIN) AF: 0.576 AC: 8447 AN: 14666

Middle Eastern (MID) AF: 0.582 AC: 226 AN: 388

European-Non Finnish (NFE) AF: 0.587 AC: 22048 AN: 37584

Other (OTH) AF: 0.546 AC: 2876 AN: 5264

GnomAD4 genome AF: 0.498 AC: 75707 AN: 152072 Hom.: 19832 Cov.: 33 AF XY: 0.501 AC XY: 37221 AN XY: 74352

African (AFR) AF: 0.317 AC: 13128 AN: 41460

American (AMR) AF: 0.520 AC: 7945 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2041 AN: 3472

East Asian (EAS) AF: 0.553 AC: 2861 AN: 5170

South Asian (SAS) AF: 0.520 AC: 2507 AN: 4824

European-Finnish (FIN) AF: 0.581 AC: 6142 AN: 10574

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39416 AN: 67974

Other (OTH) AF: 0.512 AC: 1082 AN: 2112

Alfa AF: 0.546 Hom.: 31817

Bravo AF: 0.485

Asia WGS AF: 0.518 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.9
DANN	Benign	0.68
PhyloP100		0.94
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: rs3743103; hg19: chr15-33025627; COSMIC: COSV55715066; COSMIC: COSV55715066;