15-32717891-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000558441.1(GREM1-AS1):n.1117C>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 0.01 in 438,894 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 142 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 29 hom. )

Consequence

GREM1-AS1
ENST00000558441.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.14

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

hereditary mixed polyposis syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P
polyposis syndrome, hereditary mixed, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

GREM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 15-32717891-G-T is Benign according to our data. Variant chr15-32717891-G-T is described in ClinVar as [Benign]. Clinvar id is 1253919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GREM1	NM_013372.7 link	c.-272G>T	upstream_gene_variant	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7
GREM1	NM_001191323.2 link	c.-272G>T	upstream_gene_variant		NP_001178252.1	O60565-2
GREM1	NM_001191322.2 link	c.-272G>T	upstream_gene_variant		NP_001178251.1	B3KTR9
GREM1-AS1	NR_109767.1 link	n.*210C>A	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1 link	c.-272G>T		upstream_gene_variant			NM_013372.7	ENSP00000498748.1		O60565-1
GREM1	ENST00000560677.5 link	c.-272G>T		upstream_gene_variant		4		ENSP00000453387.1		H0YLY2

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3656

AN:

151720

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0192

GnomAD4 exome

AF:

0.00251

AC:

720

AN:

287064

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

301

AN XY:

135818

show subpopulations

African (AFR)

AF:

0.0883

AC:

568

AN:

6434

American (AMR)

AF:

0.00952

AC:

AN:

1576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4332

East Asian (EAS)

AF:

0.00

AC:

AN:

8328

South Asian (SAS)

AF:

0.000186

AC:

AN:

5374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

164

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

768

European-Non Finnish (NFE)

AF:

0.000209

AC:

AN:

248418

Other (OTH)

AF:

0.00703

AC:

AN:

11670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0242

AC:

3678

AN:

151830

Hom.:

142

Cov.:

AF XY:

0.0228

AC XY:

1691

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.0842

AC:

3484

AN:

41390

American (AMR)

AF:

0.00817

AC:

125

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5086

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

67898

Other (OTH)

AF:

0.0190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

161

322

483

644

805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.0272

Asia WGS

AF:

0.00435

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

2.1

PromoterAI

0.096

Neutral

(source)

Splicing

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

Publications

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15-32717891-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over