rs186999445
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004329.3(BMPR1A):c.676-6A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,613,818 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004329.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152090Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251144Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135740
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461610Hom.: 0 Cov.: 32 AF XY: 0.0000481 AC XY: 35AN XY: 727112
GnomAD4 genome AF: 0.000138 AC: 21AN: 152208Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74410
ClinVar
Submissions by phenotype
not specified Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Generalized juvenile polyposis/juvenile polyposis coli Uncertain:1Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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not provided Benign:2
BMPR1A: BP4, BS2 -
Variant summary: The BMPR1A c.676-6A>C variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this substitution along with 5/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 14/118044 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.0002616 (3/11468). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic BMPR1A variant (0.000002), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as benign. -
Hereditary cancer-predisposing syndrome Benign:2
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Juvenile polyposis syndrome Benign:2
This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -
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BMPR1A-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at