15-32731469-C-T

Variant summary

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

The NM_013372.7(GREM1):​c.*224C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 584,906 control chromosomes in the GnomAD database, including 94,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20282 hom., cov: 31)
Exomes 𝑓: 0.58 ( 74629 hom. )

Consequence

GREM1
NM_013372.7 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.215
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 15-32731469-C-T is Benign according to our data. Variant chr15-32731469-C-T is described in ClinVar as [Benign]. Clinvar id is 1222045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GREM1NM_013372.7 linkuse as main transcriptc.*224C>T 3_prime_UTR_variant 2/2 ENST00000651154.1 NP_037504.1 O60565-1A6XAA7
GREM1NM_001368719.1 linkuse as main transcriptc.*224C>T 3_prime_UTR_variant 2/2 NP_001355648.1
GREM1NM_001191323.2 linkuse as main transcriptc.*224C>T 3_prime_UTR_variant 3/3 NP_001178252.1 O60565-2
GREM1NM_001191322.2 linkuse as main transcriptc.*224C>T 3_prime_UTR_variant 3/3 NP_001178251.1 B3KTR9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GREM1ENST00000651154.1 linkuse as main transcriptc.*224C>T 3_prime_UTR_variant 2/2 NM_013372.7 ENSP00000498748.1 O60565-1
GREM1ENST00000652365.1 linkuse as main transcriptc.*224C>T 3_prime_UTR_variant 2/2 ENSP00000498763.1 O60565-1
GREM1ENST00000560830.1 linkuse as main transcriptc.*224C>T 3_prime_UTR_variant 3/32 ENSP00000453141.1 O60565-2

Frequencies

GnomAD3 genomes
AF:
0.492
AC:
74616
AN:
151798
Hom.:
20278
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.244
Gnomad AMI
AF:
0.457
Gnomad AMR
AF:
0.522
Gnomad ASJ
AF:
0.606
Gnomad EAS
AF:
0.769
Gnomad SAS
AF:
0.618
Gnomad FIN
AF:
0.610
Gnomad MID
AF:
0.579
Gnomad NFE
AF:
0.580
Gnomad OTH
AF:
0.515
GnomAD4 exome
AF:
0.582
AC:
252042
AN:
432992
Hom.:
74629
Cov.:
2
AF XY:
0.585
AC XY:
132065
AN XY:
225844
show subpopulations
Gnomad4 AFR exome
AF:
0.236
Gnomad4 AMR exome
AF:
0.517
Gnomad4 ASJ exome
AF:
0.591
Gnomad4 EAS exome
AF:
0.704
Gnomad4 SAS exome
AF:
0.603
Gnomad4 FIN exome
AF:
0.610
Gnomad4 NFE exome
AF:
0.581
Gnomad4 OTH exome
AF:
0.571
GnomAD4 genome
AF:
0.491
AC:
74638
AN:
151914
Hom.:
20282
Cov.:
31
AF XY:
0.498
AC XY:
37004
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.243
Gnomad4 AMR
AF:
0.522
Gnomad4 ASJ
AF:
0.606
Gnomad4 EAS
AF:
0.768
Gnomad4 SAS
AF:
0.620
Gnomad4 FIN
AF:
0.610
Gnomad4 NFE
AF:
0.580
Gnomad4 OTH
AF:
0.521
Alfa
AF:
0.483
Hom.:
5171
Bravo
AF:
0.472
Asia WGS
AF:
0.638
AC:
2221
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
Benign, criteria provided, single submitterclinical testingGeneDxJul 06, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
2.9
DANN
Benign
0.53

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.

Other links and lift over

dbSNP: rs33963919; hg19: chr15-33023670; API