rs201393380
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001114753.3(ENG):āc.617G>Cā(p.Gly206Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,598,658 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. G206G) has been classified as Likely benign.
Frequency
Consequence
NM_001114753.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.617G>C | p.Gly206Ala | missense_variant | 5/15 | ENST00000373203.9 | |
ENG | NM_000118.4 | c.617G>C | p.Gly206Ala | missense_variant | 5/14 | ||
ENG | NM_001278138.2 | c.71G>C | p.Gly24Ala | missense_variant | 5/15 | ||
ENG | NM_001406715.1 | c.617G>C | p.Gly206Ala | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.617G>C | p.Gly206Ala | missense_variant | 5/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.617G>C | p.Gly206Ala | missense_variant | 5/14 | 1 | A2 | ||
ENG | ENST00000480266.6 | c.71G>C | p.Gly24Ala | missense_variant | 5/15 | 2 | |||
ENG | ENST00000462196.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000684 AC: 104AN: 152100Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000127 AC: 27AN: 213024Hom.: 0 AF XY: 0.0000855 AC XY: 10AN XY: 117000
GnomAD4 exome AF: 0.0000581 AC: 84AN: 1446558Hom.: 1 Cov.: 34 AF XY: 0.0000432 AC XY: 31AN XY: 718338
GnomAD4 genome ? AF: 0.000684 AC: 104AN: 152100Hom.: 1 Cov.: 32 AF XY: 0.000700 AC XY: 52AN XY: 74278
ClinVar
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 02, 2018 | The ENG c.617G>C; p.Gly206Ala variant (rs201393380), is reported in the literature in an individual with features of HHT but not a definitive diagnosis (Mallet 2015), and the variant did not co-segregate with disease in this family. Functional studies of the variant protein show normal localization to the cell surface and a normal BMP9 response (Mallet 2015). This variant is reported in ClinVar (Variation ID: 407133). It is found in the African population with an allele frequency of 0.3% (28/8684 alleles) in the Genome Aggregation Database. The glycine at codon 206 is well conserved, but computational algorithms (SIFT: Damaging, PolyPhen2: Benign) predict conflicting effects of this variant on the protein. Based on available information, this variant is considered likely benign. REFERENCES Mallet C et al. Functional analysis of endoglin mutations from hereditary hemorrhagic telangiectasia type 1 patients reveals different mechanisms for endoglin loss of function. Hum Mol Genet. 2015 Feb 15;24(4):1142-54. - |
Hereditary hemorrhagic telangiectasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 13, 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