Variant 15-32718535-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001368719.1(GREM1):c.-169G>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 0.246 in 454,108 control chromosomes in the GnomAD database, including 16,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5307 hom., cov: 32)

Exomes 𝑓: 0.25 ( 10811 hom. )

Consequence

GREM1
NM_001368719.1 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.129

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 15-32718535-G-A is Benign according to our data. Variant chr15-32718535-G-A is described in ClinVar as [Benign]. Clinvar id is 1240993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7 link	c.-2+374G>A		intron_variant	Intron 1 of 1	ENST00000651154.1	NP_037504.1	O60565-1A6XAA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1 link	c.-2+374G>A		intron_variant	Intron 1 of 1		NM_013372.7	ENSP00000498748.1		O60565-1
GREM1	ENST00000560677.5 link	c.-2+374G>A		intron_variant	Intron 1 of 2	4		ENSP00000453387.1		H0YLY2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37229

AN:

151936

Hom.:

5295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.0879

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.266

AC:

33897

AN:

127344

Hom.:

5768

AF XY:

0.271

AC XY:

18911

AN XY:

69888

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.697

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.247

AC:

74556

AN:

302054

Hom.:

10811

Cov.:

AF XY:

0.255

AC XY:

43781

AN XY:

171870

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.688

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.245

AC:

37278

AN:

152054

Hom.:

5307

Cov.:

AF XY:

0.250

AC XY:

18598

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.688

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.299

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.207

Hom.:

1148

Bravo

AF:

0.239

Asia WGS

AF:

0.484

AC:

1680

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27379672) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.92

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