rs138799379
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001114753.3(ENG):c.1712G>A(p.Arg571His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,614,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R571C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001114753.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1712G>A | p.Arg571His | missense_variant | 13/15 | ENST00000373203.9 | |
LOC102723566 | NR_136302.1 | n.1113C>T | non_coding_transcript_exon_variant | 1/6 | |||
ENG | NM_000118.4 | c.1712G>A | p.Arg571His | missense_variant | 13/14 | ||
ENG | NM_001278138.2 | c.1166G>A | p.Arg389His | missense_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.1712G>A | p.Arg571His | missense_variant | 13/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.1712G>A | p.Arg571His | missense_variant | 13/14 | 1 | A2 | ||
ENST00000439298.5 | n.1113C>T | non_coding_transcript_exon_variant | 1/6 | 2 | |||||
ENG | ENST00000480266.6 | c.1166G>A | p.Arg389His | missense_variant | 13/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000163 AC: 41AN: 251338Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135894
GnomAD4 exome AF: 0.000105 AC: 154AN: 1461880Hom.: 1 Cov.: 30 AF XY: 0.0000990 AC XY: 72AN XY: 727246
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74458
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 04, 2019 | - - |
Telangiectasia, hereditary hemorrhagic, type 1 Benign:1
Likely benign, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2018 | BS1 +BP2+BP6 - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 17, 2018 | 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. - |
Hereditary hemorrhagic telangiectasia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at