2-219209988-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005689.4(ABCB6):​c.2479G>A​(p.Gly827Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ABCB6
NM_005689.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32
Variant links:
Genes affected
ABCB6 (HGNC:47): (ATP binding cassette subfamily B member 6 (LAN blood group)) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. This protein is a member of the heavy metal importer subfamily and plays a role in porphyrin transport. This gene is the molecular basis of the Langereis (Lan) blood group antigen and mutations in this gene underlie familial pseudohyperkalemia and dyschromatosis universalis hereditaria. [provided by RefSeq, Mar 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23354837).
BS2
High AC in GnomAdExome4 at 41 AD,BG gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCB6NM_005689.4 linkuse as main transcriptc.2479G>A p.Gly827Arg missense_variant 19/19 ENST00000265316.9
ABCB6NM_001349828.2 linkuse as main transcriptc.2341G>A p.Gly781Arg missense_variant 18/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCB6ENST00000265316.9 linkuse as main transcriptc.2479G>A p.Gly827Arg missense_variant 19/191 NM_005689.4 P1Q9NP58-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000280
AC:
41
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.0000179
AC XY:
13
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
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:
0.0000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 16, 2021The c.2479G>A (p.G827R) alteration is located in exon 19 (coding exon 19) of the ABCB6 gene. This alteration results from a G to A substitution at nucleotide position 2479, causing the glycine (G) at amino acid position 827 to be replaced by an arginine (R). 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
0.13
BayesDel_addAF
Uncertain
0.031
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.042
T;.
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.079
D
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
0.73
N;.
MutationTaster
Benign
0.95
D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
0.030
N;.
REVEL
Uncertain
0.32
Sift
Benign
0.23
T;.
Sift4G
Benign
0.49
T;.
Polyphen
0.74
P;P
Vest4
0.20
MutPred
0.22
Gain of solvent accessibility (P = 0.019);.;
MVP
0.92
MPC
0.26
ClinPred
0.53
D
GERP RS
5.7
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.7
Varity_R
0.17
gMVP
0.50

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: rs780047348; hg19: chr2-220074710; API