Variant chr15-32718052-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013372.7(GREM1):c.-111G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,168,238 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00067 ( 3 hom. )

Consequence

GREM1
NM_013372.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.57

Variant links:

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 links:

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

GREM1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 15-32718052-G-A is Benign according to our data. Variant chr15-32718052-G-A is described in ClinVar as [Benign]. Clinvar id is 1697735.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 634 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GREM1	NM_013372.7 linkuse as main transcript	c.-111G>A	5_prime_UTR_variant	1/2	ENST00000651154.1
GREM1	NM_001191322.2 linkuse as main transcript	c.-111G>A	5_prime_UTR_variant	1/3
GREM1	NM_001191323.2 linkuse as main transcript	c.-111G>A	5_prime_UTR_variant	1/3
GREM1-AS1	NR_109767.1 linkuse as main transcript		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREM1	ENST00000651154.1 linkuse as main transcript	c.-111G>A		5_prime_UTR_variant	1/2		NM_013372.7	P1	O60565-1
GREM1-AS1	ENST00000558441.1 linkuse as main transcript	n.956C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

624

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00108

AC:

AN:

8366

Hom.:

AF XY:

0.00159

AC XY:

AN XY:

4410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000720

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000671

AC:

682

AN:

1016180

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

287

AN XY:

479922

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.00365

Gnomad4 ASJ exome

AF:

0.000341

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000703

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00417

AC:

634

AN:

152058

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

280

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00409

Hom.:

Bravo

AF:

0.00479

Asia WGS

AF:

0.00145

AC:

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

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

-0.67

CADD

Benign

2.7

DANN

Benign

0.96

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

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