12-122980428-G-A

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

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.802
Variant links:
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]

Genome browser will be placed here

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
ARL6IP4NM_001400282.1 linkuse as main transcriptc.-12+43G>A intron_variant NP_001387211.1
ARL6IP4NM_001400320.1 linkuse as main transcriptc.-12+43G>A intron_variant NP_001387249.1
ARL6IP4NM_001400283.1 linkuse as main transcriptc.-12+43G>A intron_variant NP_001387212.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCB9ENST00000542678.5 linkuse as main transcriptc.-1618C>T 5_prime_UTR_variant 1/121 ENSP00000440288.1 Q9NP78-1
ARL6IP4ENST00000453766 linkuse as main transcriptc.-329G>A 5_prime_UTR_variant 1/61 ENSP00000414847.4 F8WCT1
ARL6IP4ENST00000543566 linkuse as main transcriptc.-329G>A 5_prime_UTR_variant 1/61 ENSP00000442718.3 Q66PJ3-9A0A0C4DG62

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000362
AC:
3
AN:
82968
Hom.:
0
AF XY:
0.0000215
AC XY:
1
AN XY:
46548
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000368
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000331
AC:
4
AN:
1209314
Hom.:
0
Cov.:
31
AF XY:
0.00000171
AC XY:
1
AN XY:
585420
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000182
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000204
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152224
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000267
AC:
3

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 submitterclinical testingAmbry GeneticsMay 18, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
0.85
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0018
T;.;.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.59
T;T;T;T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.043
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;N;.;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.050
.;.;.;N;.
REVEL
Benign
0.13
Sift
Pathogenic
0.0
.;.;.;D;.
Sift4G
Benign
0.11
T;T;T;D;T
Vest4
0.16
MVP
0.040
MPC
0.98
ClinPred
0.13
T
GERP RS
-5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.028
gMVP
0.038

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs767540748; hg19: chr12-123464975; API