rs12915554
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_013372.7(GREM1):c.*40C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,505,728 control chromosomes in the GnomAD database, including 83,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.26 ( 6387 hom., cov: 31)
Exomes 𝑓: 0.33 ( 77124 hom. )
Consequence
GREM1
NM_013372.7 3_prime_UTR
NM_013372.7 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.580
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 15-32731285-C-A is Benign according to our data. Variant chr15-32731285-C-A is described in ClinVar as [Benign]. Clinvar id is 1282623.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GREM1 | NM_013372.7 | c.*40C>A | 3_prime_UTR_variant | 2/2 | ENST00000651154.1 | ||
GREM1 | NM_001191322.2 | c.*40C>A | 3_prime_UTR_variant | 3/3 | |||
GREM1 | NM_001191323.2 | c.*40C>A | 3_prime_UTR_variant | 3/3 | |||
GREM1 | NM_001368719.1 | c.*40C>A | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GREM1 | ENST00000651154.1 | c.*40C>A | 3_prime_UTR_variant | 2/2 | NM_013372.7 | P1 | |||
GREM1 | ENST00000560830.1 | c.*40C>A | 3_prime_UTR_variant | 3/3 | 2 | ||||
GREM1 | ENST00000652365.1 | c.*40C>A | 3_prime_UTR_variant | 2/2 | P1 | ||||
GREM1 | ENST00000560677.5 | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.264 AC: 40125AN: 151932Hom.: 6384 Cov.: 31
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GnomAD3 exomes AF: 0.288 AC: 63702AN: 221372Hom.: 10275 AF XY: 0.293 AC XY: 34644AN XY: 118134
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GnomAD4 exome AF: 0.328 AC: 444298AN: 1353676Hom.: 77124 Cov.: 20 AF XY: 0.327 AC XY: 220263AN XY: 673456
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GnomAD4 genome ? AF: 0.264 AC: 40135AN: 152052Hom.: 6387 Cov.: 31 AF XY: 0.262 AC XY: 19507AN XY: 74320
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 14, 2018 | This variant is associated with the following publications: (PMID: 28977865) - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at