12-122980428-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000542678.5(ABCB9):c.-1618C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000367 in 1,361,538 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000033 ( 0 hom. )
Consequence
ABCB9
ENST00000542678.5 5_prime_UTR
ENST00000542678.5 5_prime_UTR
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: -0.802
Genes affected
ABCB9 (HGNC:50): (ATP binding cassette subfamily B member 9) 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 as well as antigen presentation. This family member functions in the translocation of peptides from the cytosol into the lysosomal lumen. Alternative splicing of this gene results in distinct isoforms which are likely to have different substrate specificities. [provided by RefSeq, Jul 2011]
ARL6IP4 (HGNC:18076): (ADP ribosylation factor like GTPase 6 interacting protein 4) Enables identical protein binding activity. Predicted to be involved in RNA splicing and mRNA processing. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042917997).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARL6IP4 | NM_001400282.1 | c.-12+43G>A | intron_variant | NP_001387211.1 | ||||
ARL6IP4 | NM_001400320.1 | c.-12+43G>A | intron_variant | NP_001387249.1 | ||||
ARL6IP4 | NM_001400283.1 | c.-12+43G>A | intron_variant | NP_001387212.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCB9 | ENST00000542678.5 | c.-1618C>T | 5_prime_UTR_variant | 1/12 | 1 | ENSP00000440288.1 | ||||
ARL6IP4 | ENST00000453766 | c.-329G>A | 5_prime_UTR_variant | 1/6 | 1 | ENSP00000414847.4 | ||||
ARL6IP4 | ENST00000543566 | c.-329G>A | 5_prime_UTR_variant | 1/6 | 1 | ENSP00000442718.3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000362 AC: 3AN: 82968Hom.: 0 AF XY: 0.0000215 AC XY: 1AN XY: 46548
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GnomAD4 exome AF: 0.00000331 AC: 4AN: 1209314Hom.: 0 Cov.: 31 AF XY: 0.00000171 AC XY: 1AN XY: 585420
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2022 | The c.41G>A (p.R14H) alteration is located in exon 1 (coding exon 1) of the ARL6IP4 gene. This alteration results from a G to A substitution at nucleotide position 41, causing the arginine (R) at amino acid position 14 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;N
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;.;N;.
REVEL
Benign
Sift
Pathogenic
.;.;.;D;.
Sift4G
Benign
T;T;T;D;T
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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