chr2-168923202-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003742.4(ABCB11):c.*420A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 175,774 control chromosomes in the GnomAD database, including 22,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.48 ( 18879 hom., cov: 32)
Exomes 𝑓: 0.50 ( 3236 hom. )
Consequence
ABCB11
NM_003742.4 3_prime_UTR
NM_003742.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.236
Genes affected
ABCB11 (HGNC:42): (ATP binding cassette subfamily B member 11) 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 the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [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=-0.91).
BP6
Variant 2-168923202-T-C is Benign according to our data. Variant chr2-168923202-T-C is described in ClinVar as [Benign]. Clinvar id is 332013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCB11 | NM_003742.4 | c.*420A>G | 3_prime_UTR_variant | 28/28 | ENST00000650372.1 | ||
ABCB11 | XM_011512078.3 | c.*374A>G | 3_prime_UTR_variant | 29/29 | |||
ABCB11 | XM_017005165.2 | c.3867+1455A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB11 | ENST00000650372.1 | c.*420A>G | 3_prime_UTR_variant | 28/28 | NM_003742.4 | P1 | |||
ABCB11 | ENST00000649448.1 | c.*420A>G | 3_prime_UTR_variant | 15/15 | |||||
ABCB11 | ENST00000648875.1 | c.226+1455A>G | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.483 AC: 73358AN: 151866Hom.: 18880 Cov.: 32
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GnomAD4 exome AF: 0.505 AC: 12005AN: 23790Hom.: 3236 Cov.: 0 AF XY: 0.511 AC XY: 6275AN XY: 12274
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GnomAD4 genome AF: 0.483 AC: 73380AN: 151984Hom.: 18879 Cov.: 32 AF XY: 0.490 AC XY: 36396AN XY: 74282
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Progressive familial intrahepatic cholestasis type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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