chr15-32729889-G-A

Position:

• chr15-32729889-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013372.7(GREM1):​c.-1-801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,210 control chromosomes in the GnomAD database, including 2,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2832 hom., cov: 33)
• Consequence: GREM1 NM_013372.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 15-32729889-G-A is Benign according to our data. Variant chr15-32729889-G-A is described in ClinVar as [Benign]. Clinvar id is 1288795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-1-801G>A		intron_variant		ENST00000651154.1	NP_037504.1
GREM1	NM_001191322.2	c.-1-801G>A		intron_variant			NP_001178251.1
GREM1	NM_001191323.2	c.-1-801G>A		intron_variant			NP_001178252.1
GREM1	NM_001368719.1	c.-1-801G>A		intron_variant			NP_001355648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-1-801G>A		intron_variant			NM_013372.7	ENSP00000498748	P1
GREM1	ENST00000560677.5	c.-1-801G>A		intron_variant		4		ENSP00000453387
GREM1	ENST00000560830.1	c.-1-801G>A		intron_variant		2		ENSP00000453141
GREM1	ENST00000652365.1	c.-1-801G>A		intron_variant				ENSP00000498763	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25210 AN: 152092 Hom.: 2831 Cov.: 33

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.166 AC: 25213 AN: 152210 Hom.: 2832 Cov.: 33 AF XY: 0.172 AC XY: 12773 AN XY: 74410

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.180

Alfa AF: 0.179 Hom.: 750

Bravo AF: 0.154

Asia WGS AF: 0.382 AC: 1326 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.8
DANN	Benign	0.85

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: rs35330276; hg19: chr15-33022090;