rs1555520951
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001171.6(ABCC6):c.662+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 137,152 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001171.6 intron
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.662+12C>T | intron_variant | Intron 6 of 30 | ENST00000205557.12 | NP_001162.5 | ||
ABCC6 | NM_001351800.1 | c.320+12C>T | intron_variant | Intron 6 of 30 | NP_001338729.1 | |||
ABCC6 | NR_147784.1 | n.699+12C>T | intron_variant | Intron 6 of 28 | ||||
LOC105371100 | XR_933131.3 | n.282+82G>A | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0183 AC: 2510AN: 137078Hom.: 43 Cov.: 23
GnomAD3 exomes AF: 0.0166 AC: 2389AN: 143728Hom.: 35 AF XY: 0.0168 AC XY: 1289AN XY: 76952
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0244 AC: 16526AN: 678232Hom.: 314 Cov.: 9 AF XY: 0.0241 AC XY: 8707AN XY: 361336
GnomAD4 genome AF: 0.0183 AC: 2513AN: 137152Hom.: 43 Cov.: 23 AF XY: 0.0169 AC XY: 1120AN XY: 66356
ClinVar
Submissions by phenotype
not provided Benign:2
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The ABCC6 c.662+12C>T variant was not identified in the literature nor was it identified in the Cosmic database. The variant was identified in dbSNP (ID: rs72664291), ClinVar (reported likely benign by GeneDx and pathogenic by PXE International), Clinvitae, and LOVD 3.0 (classified as benign). The variant was identified in control databases in 2838 of 169536 chromosomes (42 homozygous) at a frequency of 0.01674 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 1691 of 65948 chromosomes (freq: 0.02564), Other in 93 of 4902 chromosomes (freq: 0.01897), European (Finnish) in 326 of 18338 chromosomes (freq: 0.01778), South Asian in 310 of 21710 chromosomes (freq: 0.01428), Ashkenazi Jewish in 103 of 7726 chromosomes (freq: 0.01333), Latino in 256 of 24756 chromosomes (freq: 0.01034), African in 44 of 13714 chromosomes (freq: 0.003208), and East Asian in 15 of 12442 chromosomes (freq: 0.001206). The c.662+12C>T variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, and GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
not specified Benign:1
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. -
Autosomal recessive inherited pseudoxanthoma elasticum Benign:1
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Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at