rs369709495
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_022436.3(ABCG5):c.1410C>T(p.His470His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000081 ( 0 hom. )
Consequence
ABCG5
NM_022436.3 synonymous
NM_022436.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0900
Genes affected
ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) 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). This protein is a member of the White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]
DYNC2LI1 (HGNC:24595): (dynein cytoplasmic 2 light intermediate chain 1) This gene encodes a protein that is a component of the dynein-2 microtubule motor protein complex that plays a role in the retrograde transport of cargo in primary cilia via the intraflagellar transport system. This gene is ubiquitously expressed and its protein, which localizes to the axoneme and Golgi apparatus, interacts directly with the cytoplasmic dynein 2 heavy chain 1 protein to form part of the multi-protein dynein-2 complex. Mutations in this gene produce defects in the dynein-2 complex which result in several types of ciliopathy including short-rib thoracic dysplasia 15 with polydactyly (SRTD15). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 2-43822850-G-A is Benign according to our data. Variant chr2-43822850-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 529882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-43822850-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.09 with no splicing effect.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCG5 | ENST00000405322.8 | c.1410C>T | p.His470His | synonymous_variant | 10/13 | 1 | NM_022436.3 | ENSP00000384513.2 | ||
ABCG5 | ENST00000486512.5 | n.1931C>T | non_coding_transcript_exon_variant | 6/9 | 1 | |||||
ABCG5 | ENST00000409962.1 | n.1693C>T | non_coding_transcript_exon_variant | 6/9 | 2 | |||||
ABCG5 | ENST00000644754.1 | n.1794C>T | non_coding_transcript_exon_variant | 7/10 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000107 AC: 27AN: 251268Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135834
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GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.0000756 AC XY: 55AN XY: 727230
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Sitosterolemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 09, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2019 | 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at