rs7176378

Variant names:

• chr15-32734978-T-A
• rs7176378
• NM_013372.7:c.*3733T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-32734978-T-A
• chr15-32734978-T-C
• chr15-32734978-T-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.*3733T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 154,388 control chromosomes in the GnomAD database, including 50,553 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 0.81 (49842 hom., cov: 31)
  • Exomes 𝑓: 0.80 (711 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 3 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, Orphanet, G2P
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.*3733T>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000651154.1	NP_037504.1
GREM1	NM_001368719.1	c.*3733T>A		3_prime_UTR_variant	Exon 2 of 2		NP_001355648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.*3733T>A		3_prime_UTR_variant	Exon 2 of 2		NM_013372.7	ENSP00000498748.1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122386 AN: 152034 Hom.: 49786 Cov.: 31

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.782

GnomAD4 exome AF: 0.797 AC: 1781 AN: 2236 Hom.: 711 Cov.: 0 AF XY: 0.795 AC XY: 808 AN XY: 1016

African (AFR) AF: 0.853 AC: 58 AN: 68

American (AMR) AF: 0.795 AC: 35 AN: 44

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 114 AN: 158

East Asian (EAS) AF: 0.998 AC: 435 AN: 436

South Asian (SAS) AF: 0.818 AC: 18 AN: 22

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.833 AC: 10 AN: 12

European-Non Finnish (NFE) AF: 0.744 AC: 966 AN: 1298

Other (OTH) AF: 0.732 AC: 145 AN: 198

GnomAD4 genome AF: 0.805 AC: 122502 AN: 152152 Hom.: 49842 Cov.: 31 AF XY: 0.811 AC XY: 60287 AN XY: 74382

African (AFR) AF: 0.898 AC: 37287 AN: 41526

American (AMR) AF: 0.819 AC: 12529 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2603 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5160 AN: 5176

South Asian (SAS) AF: 0.852 AC: 4097 AN: 4806

European-Finnish (FIN) AF: 0.814 AC: 8617 AN: 10592

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49552 AN: 67974

Other (OTH) AF: 0.784 AC: 1660 AN: 2116

Alfa AF: 0.770 Hom.: 5627

Bravo AF: 0.810

Asia WGS AF: 0.910 AC: 3165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		0.16

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: rs7176378; hg19: chr15-33027179;