Variant chr15-32717971-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000558441.1(GREM1-AS1):n.1037C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,052,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

GREM1-AS1
ENST00000558441.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620

Variant links:

Genes affected

GREM1-AS1 (HGNC:):

GREM1-AS1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 15-32717971-G-T is Benign according to our data. Variant chr15-32717971-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1802876.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
	use as main transcript	n.32717971G>T	intergenic_region
GREM1	NM_013372.7 linkuse as main transcript	c.-192G>T	upstream_gene_variant	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001191323.2 linkuse as main transcript	c.-192G>T	upstream_gene_variant		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 linkuse as main transcript	c.-192G>T	upstream_gene_variant		NP_001178251.1	B3KTR9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GREM1-AS1	ENST00000558441.1 linkuse as main transcript	n.1037C>A	non_coding_transcript_exon_variant	1/1	6
GREM1	ENST00000651154.1 linkuse as main transcript	c.-192G>T	upstream_gene_variant			NM_013372.7	ENSP00000498748.1	O60565-1
GREM1	ENST00000560677.5 linkuse as main transcript	c.-192G>T	upstream_gene_variant		4		ENSP00000453387.1	H0YLY2
GREM1	ENST00000560830.1 linkuse as main transcript	c.-192G>T	upstream_gene_variant		2		ENSP00000453141.1	O60565-2

Frequencies

GnomAD3 genomes

AF:

0.000303

AC:

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00369

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.0000799

AC:

AN:

901138

Hom.:

Cov.:

AF XY:

0.0000985

AC XY:

AN XY:

416434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000883

Gnomad4 OTH exome

AF:

0.0000304

GnomAD4 genome

AF:

0.000303

AC:

AN:

151820

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00369

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over