rs72657698
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001171.6(ABCC6):āc.793A>Gā(p.Arg265Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 151,816 control chromosomes in the GnomAD database, including 358 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_001171.6 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.793A>G | p.Arg265Gly | missense_variant, splice_region_variant | 7/31 | ENST00000205557.12 | |
ABCC6 | NM_001351800.1 | c.451A>G | p.Arg151Gly | missense_variant, splice_region_variant | 7/31 | ||
ABCC6 | NR_147784.1 | n.830A>G | splice_region_variant, non_coding_transcript_exon_variant | 7/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.793A>G | p.Arg265Gly | missense_variant, splice_region_variant | 7/31 | 1 | NM_001171.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0666 AC: 10110AN: 151698Hom.: 359 Cov.: 30
GnomAD3 exomes AF: 0.0427 AC: 10355AN: 242738Hom.: 511 AF XY: 0.0431 AC XY: 5647AN XY: 131142
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0366 AC: 49797AN: 1360146Hom.: 3822 Cov.: 33 AF XY: 0.0372 AC XY: 25224AN XY: 678628
GnomAD4 genome ? AF: 0.0666 AC: 10108AN: 151816Hom.: 358 Cov.: 30 AF XY: 0.0644 AC XY: 4777AN XY: 74192
ClinVar
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | research | PXE International | Mar 01, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 29, 2015 | This variant was found once in our laboratory in trans with a pathogenic variant [R518X] in a 39-year-old male with hereditary anemia, angioid streaks on retina, possible pseudoxanthoma elasticum, fatigue, chronic joint pain. However, variant is common, and we have identified homozygotes who do not have features of PXE. - |
not provided Benign:3
Likely benign, no assertion criteria provided | literature only | Department of Ophthalmology and Visual Sciences Kyoto University | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 19726431, 27884173, 11536079, 16086317, 19339160, 33144682) - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2022 | This alteration is classified as 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. - |
Pseudoxanthoma elasticum, forme fruste Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Arterial calcification, generalized, of infancy, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 29, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at