chr12-54281950-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_031157.4(HNRNPA1):c.279+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HNRNPA1
NM_031157.4 intron
NM_031157.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.896
Genes affected
HNRNPA1 (HGNC:5031): (heterogeneous nuclear ribonucleoprotein A1) This gene encodes a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs), which are RNA-binding proteins that associate with pre-mRNAs in the nucleus and influence pre-mRNA processing, as well as other aspects of mRNA metabolism and transport. The protein encoded by this gene is one of the most abundant core proteins of hnRNP complexes and plays a key role in the regulation of alternative splicing. Mutations in this gene have been observed in individuals with amyotrophic lateral sclerosis 20. Multiple alternatively spliced transcript variants have been found. There are numerous pseudogenes of this gene distributed throughout the genome. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 12-54281950-G-A is Benign according to our data. Variant chr12-54281950-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3048056.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000548 (8/1460014) while in subpopulation SAS AF= 0.0000812 (7/86208). AF 95% confidence interval is 0.0000377. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPA1 | NM_031157.4 | c.279+9G>A | intron_variant | ENST00000340913.11 | |||
HNRNPA1 | NM_002136.4 | c.279+9G>A | intron_variant | ||||
HNRNPA1 | NR_135167.2 | n.361+9G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPA1 | ENST00000340913.11 | c.279+9G>A | intron_variant | 1 | NM_031157.4 | ||||
ENST00000553061.1 | n.545+4775G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 151932Hom.: 0 Cov.: 32 FAILED QC
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GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245396Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133642
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460014Hom.: 0 Cov.: 32 AF XY: 0.00000964 AC XY: 7AN XY: 726374
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 151932Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74198
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HNRNPA1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 01, 2023 | 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
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at