chr12-54282620-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2
The NM_031157.4(HNRNPA1):c.631G>A(p.Gly211Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00034 in 1,613,916 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 2 hom. )
Consequence
HNRNPA1
NM_031157.4 missense
NM_031157.4 missense
Scores
8
9
Clinical Significance
Conservation
PhyloP100: 4.96
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 -13 ACMG points.
PP2
Missense variant where missense usually causes diseases, HNRNPA1
BP4
Computational evidence support a benign effect (MetaRNN=0.009534627).
BP6
Variant 12-54282620-G-A is Benign according to our data. Variant chr12-54282620-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 706889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-54282620-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000572 (87/152182) while in subpopulation AMR AF= 0.000785 (12/15282). AF 95% confidence interval is 0.000452. There are 0 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 87 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPA1 | NM_031157.4 | c.631G>A | p.Gly211Ser | missense_variant | 6/11 | ENST00000340913.11 | |
HNRNPA1 | NM_002136.4 | c.631G>A | p.Gly211Ser | missense_variant | 6/10 | ||
HNRNPA1 | NR_135167.2 | n.713G>A | non_coding_transcript_exon_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPA1 | ENST00000340913.11 | c.631G>A | p.Gly211Ser | missense_variant | 6/11 | 1 | NM_031157.4 | ||
ENST00000553061.1 | n.545+5445G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000572 AC: 87AN: 152064Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000593 AC: 149AN: 251168Hom.: 0 AF XY: 0.000545 AC XY: 74AN XY: 135826
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GnomAD4 exome AF: 0.000315 AC: 461AN: 1461734Hom.: 2 Cov.: 31 AF XY: 0.000303 AC XY: 220AN XY: 727182
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GnomAD4 genome AF: 0.000572 AC: 87AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000726 AC XY: 54AN XY: 74420
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;D;D
Polyphen
P;P;P;.;.
Vest4
MVP
MPC
0.49
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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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