Variant 15-32717967-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000558441.1(GREM1-AS1):n.1041G>C 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 0.000637 in 1,051,416 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

GREM1-AS1
ENST00000558441.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.791

Variant links:

Genes affected

GREM1-AS1 (HGNC:55411): (GREM1 antisense RNA 1)

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 Benign. Variant got -8 ACMG points.

BP4

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

BP6

Variant 15-32717967-C-G is Benign according to our data. Variant chr15-32717967-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2576286.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	Effect	MANE	Protein
GREM1	NM_013372.7 linkuse as main transcript	upstream_gene_variant	ENST00000651154.1	NP_037504.1
GREM1	NM_001191322.2 linkuse as main transcript	upstream_gene_variant		NP_001178251.1
GREM1	NM_001191323.2 linkuse as main transcript	upstream_gene_variant		NP_001178252.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM1-AS1	ENST00000558441.1 linkuse as main transcript	n.1041G>C	non_coding_transcript_exon_variant	1/1
GREM1	ENST00000651154.1 linkuse as main transcript		upstream_gene_variant			NM_013372.7	ENSP00000498748	P1	O60565-1
GREM1	ENST00000560677.5 linkuse as main transcript		upstream_gene_variant		4		ENSP00000453387
GREM1	ENST00000560830.1 linkuse as main transcript		upstream_gene_variant		2		ENSP00000453141		O60565-2

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

377

AN:

151798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000318

AC:

286

AN:

899510

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

142

AN XY:

415732

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.00107

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:

0.0000449

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00253

AC:

384

AN:

151906

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.00878

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000278

Hom.:

Asia WGS

AF:

0.00203

AC:

AN:

3460

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

0.88

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