rs3213471
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001171.6(ABCC6):c.3507-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,613,748 control chromosomes in the GnomAD database, including 1,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.049 ( 442 hom., cov: 32)
Exomes 𝑓: 0.016 ( 620 hom. )
Consequence
ABCC6
NM_001171.6 splice_polypyrimidine_tract, intron
NM_001171.6 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.139
Genes affected
ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 16-16161580-A-G is Benign according to our data. Variant chr16-16161580-A-G is described in ClinVar as [Benign]. Clinvar id is 433392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16161580-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.3507-16T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000205557.12 | |||
ABCC6 | NM_001351800.1 | c.3165-16T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
ABCC6 | NR_147784.1 | n.3169-16T>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.3507-16T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001171.6 | P1 | |||
ABCC6 | ENST00000456970.6 | c.*516-16T>C | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 | |||||
ABCC6 | ENST00000622290.5 | c.3507-16T>C | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0484 AC: 7363AN: 152136Hom.: 435 Cov.: 32
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GnomAD3 exomes AF: 0.0254 AC: 6335AN: 249622Hom.: 250 AF XY: 0.0232 AC XY: 3133AN XY: 135228
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GnomAD4 exome AF: 0.0159 AC: 23170AN: 1461494Hom.: 620 Cov.: 34 AF XY: 0.0157 AC XY: 11389AN XY: 727026
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GnomAD4 genome ? AF: 0.0485 AC: 7391AN: 152254Hom.: 442 Cov.: 32 AF XY: 0.0474 AC XY: 3527AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | research | PXE International | Mar 01, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Arterial calcification, generalized, of infancy, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Pseudoxanthoma elasticum, forme fruste Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at