3-129061508-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP7BA1
This summary comes from the ClinGen Evidence Repository: The c.-124C>T variant in GP9 is a non-coding variant which located upstream of the 5' UTR. It was identified through an ICLS predisposition screen in an ostensibly healthy population. To date, this variant has not been reported in any patients with BSS. The c.-124C>T variant is an intronic variant that is not predicted by SpliceAI to impact splicing (acceptor gain score of 0.1 which is less than the VCEP threshold of <0.2). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of 0.314583 (<1.5) (BP7). The Grpmax Filtering allele frequency in gnomAD v4.1 is 0.004120 (248/54052 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.001), and therefore meets this criterion (BA1).In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA82551874/MONDO:0009276/083
Frequency
Consequence
NM_000174.5 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GP9 | NM_000174.5 | c.-124C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 3 | ENST00000307395.5 | NP_000165.1 | ||
GP9 | NM_000174.5 | c.-124C>T | 5_prime_UTR_variant | Exon 2 of 3 | ENST00000307395.5 | NP_000165.1 | ||
GP9 | XM_005247374.4 | c.343C>T | p.Arg115Trp | missense_variant | Exon 4 of 4 | XP_005247431.2 | ||
GP9 | XM_047447997.1 | c.-12-220C>T | intron_variant | Intron 1 of 1 | XP_047303953.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GP9 | ENST00000307395 | c.-124C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 3 | 1 | NM_000174.5 | ENSP00000303942.4 | |||
GP9 | ENST00000307395 | c.-124C>T | 5_prime_UTR_variant | Exon 2 of 3 | 1 | NM_000174.5 | ENSP00000303942.4 |
Frequencies
GnomAD3 genomes AF: 0.00149 AC: 226AN: 152146Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.000428 AC: 192AN: 448578Hom.: 0 Cov.: 3 AF XY: 0.000393 AC XY: 93AN XY: 236424
GnomAD4 genome AF: 0.00148 AC: 226AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.00140 AC XY: 104AN XY: 74446
ClinVar
Submissions by phenotype
Bernard Soulier syndrome Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at