rs34944927

Variant names:

• chr15-32725044-GC-G
• rs34944927
• NM_013372.7:c.-1-5645delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013372.7(GREM1):​c.-1-5645delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (19565 hom., cov: 0)
• Consequence: GREM1 NM_013372.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.297
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 15-32725044-GC-G is Benign according to our data. Variant chr15-32725044-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1178065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-1-5645delC		intron_variant	Intron 1 of 1	ENST00000651154.1	NP_037504.1
GREM1	NM_001368719.1	c.-1-5645delC		intron_variant	Intron 1 of 1		NP_001355648.1
GREM1	NM_001191323.2	c.-1-5645delC		intron_variant	Intron 1 of 2		NP_001178252.1
GREM1	NM_001191322.2	c.-1-5645delC		intron_variant	Intron 1 of 2		NP_001178251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-1-5645delC		intron_variant	Intron 1 of 1		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-1-5645delC		intron_variant	Intron 1 of 2	4		ENSP00000453387.1
GREM1	ENST00000652365.1	c.-1-5645delC		intron_variant	Intron 1 of 1			ENSP00000498763.1
GREM1	ENST00000560830.1	c.-1-5645delC		intron_variant	Intron 1 of 2	2		ENSP00000453141.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74891 AN: 151726 Hom.: 19561 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.493 AC: 74923 AN: 151846 Hom.: 19565 Cov.: 0 AF XY: 0.496 AC XY: 36815 AN XY: 74188

African (AFR) AF: 0.303 AC: 12541 AN: 41404

American (AMR) AF: 0.524 AC: 7999 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2040 AN: 3464

East Asian (EAS) AF: 0.552 AC: 2836 AN: 5142

South Asian (SAS) AF: 0.541 AC: 2602 AN: 4812

European-Finnish (FIN) AF: 0.572 AC: 6023 AN: 10536

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39193 AN: 67902

Other (OTH) AF: 0.520 AC: 1100 AN: 2114

Alfa AF: 0.394 Hom.: 1088

Bravo AF: 0.479

Asia WGS AF: 0.518 AC: 1804 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=92/8	polymorphism

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: rs34944927; hg19: chr15-33017245;