rs2235012
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_001348946.2(ABCB1):c.1662G>C(p.Leu554=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000693 in 1,614,202 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 8 hom. )
Consequence
ABCB1
NM_001348946.2 synonymous
NM_001348946.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0390
Genes affected
ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated 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 MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 7-87549411-C-G is Benign according to our data. Variant chr7-87549411-C-G is described in ClinVar as [Benign]. Clinvar id is 729680.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.039 with no splicing effect.
BS2
?
High AC in GnomAd at 523 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCB1 | NM_001348946.2 | c.1662G>C | p.Leu554= | synonymous_variant | 14/28 | ENST00000622132.5 | |
ABCB1 | NM_001348945.2 | c.1872G>C | p.Leu624= | synonymous_variant | 18/32 | ||
ABCB1 | NM_000927.5 | c.1662G>C | p.Leu554= | synonymous_variant | 15/29 | ||
ABCB1 | NM_001348944.2 | c.1662G>C | p.Leu554= | synonymous_variant | 16/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB1 | ENST00000622132.5 | c.1662G>C | p.Leu554= | synonymous_variant | 14/28 | 1 | NM_001348946.2 | P1 | |
ABCB1 | ENST00000265724.8 | c.1662G>C | p.Leu554= | synonymous_variant | 15/29 | 1 | P1 | ||
ABCB1 | ENST00000543898.5 | c.1470G>C | p.Leu490= | synonymous_variant | 14/28 | 5 | |||
ABCB1 | ENST00000482527.1 | n.416G>C | non_coding_transcript_exon_variant | 2/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00344 AC: 523AN: 152190Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000839 AC: 211AN: 251474Hom.: 1 AF XY: 0.000714 AC XY: 97AN XY: 135908
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GnomAD4 exome AF: 0.000404 AC: 591AN: 1461894Hom.: 8 Cov.: 33 AF XY: 0.000364 AC XY: 265AN XY: 727248
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GnomAD4 genome ? AF: 0.00347 AC: 528AN: 152308Hom.: 3 Cov.: 32 AF XY: 0.00324 AC XY: 241AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2018 | - - |
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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at