15-32719539-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013372.7(GREM1):c.-2+1383del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,838 control chromosomes in the GnomAD database, including 6,601 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6601 hom., cov: 23)
• Consequence: GREM1 NM_013372.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00600

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 -10 ACMG points.

• BP6: Variant 15-32719539-TC-T is Benign according to our data. Variant chr15-32719539-TC-T is described in ClinVar as [Benign]. Clinvar id is 1286829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GREM1	NM_013372.7	c.-2+1383del		intron_variant		ENST00000651154.1
GREM1	NM_001191322.2	c.-2+1383del		intron_variant
GREM1	NM_001191323.2	c.-2+1383del		intron_variant
GREM1	NM_001368719.1	c.-2+842del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREM1	ENST00000651154.1	c.-2+1383del		intron_variant			NM_013372.7	P1
GREM1	ENST00000560677.5	c.-2+1383del		intron_variant		4
GREM1	ENST00000560830.1	c.-2+1383del		intron_variant		2
GREM1	ENST00000652365.1	c.-2+842del		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41479 AN: 151720 Hom.: 6587 Cov.: 23

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.274 AC: 41535 AN: 151838 Hom.: 6601 Cov.: 23 AF XY: 0.278 AC XY: 20619 AN XY: 74196

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.264

Alfa AF: 0.237 Hom.: 570

Bravo AF: 0.271

Asia WGS AF: 0.490 AC: 1705 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

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs72360084; hg19: chr15-33011740;