rs57467915

chr2-219216694-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005689.4(ABCB6):c.826C>T(p.Arg276Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,585,890 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R276Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0094 ( 13 hom., cov: 32)

Exomes 𝑓: 0.013 ( 151 hom. )

Consequence

ABCB6
NM_005689.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.12

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]

ABCB6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010985106).

BP6

Variant 2-219216694-G-A is Benign according to our data. Variant chr2-219216694-G-A is described in ClinVar as [Benign]. Clinvar id is 235291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219216694-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00938 (1428/152236) while in subpopulation NFE AF= 0.0138 (940/68010). AF 95% confidence interval is 0.0131. There are 13 homozygotes in gnomad4. There are 722 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 1427 AD,BG gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB6	NM_005689.4 linkuse as main transcript	c.826C>T	p.Arg276Trp	missense_variant	3/19	ENST00000265316.9
ABCB6	NM_001349828.2 linkuse as main transcript	c.688C>T	p.Arg230Trp	missense_variant	2/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB6	ENST00000265316.9 linkuse as main transcript	c.826C>T	p.Arg276Trp	missense_variant	3/19	1	NM_005689.4	P1	Q9NP58-1

Frequencies

GnomAD3 genomes

AF:

0.00938

AC:

1427

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00266

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00878

AC:

1807

AN:

205742

Hom.:

AF XY:

0.00871

AC XY:

969

AN XY:

111222

show subpopulations

Gnomad AFR exome

AF:

0.00268

Gnomad AMR exome

AF:

0.00346

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.0000671

Gnomad SAS exome

AF:

0.00297

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.00678

GnomAD4 exome

AF:

0.0125

AC:

17964

AN:

1433654

Hom.:

151

Cov.:

AF XY:

0.0121

AC XY:

8634

AN XY:

710922

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00388

Gnomad4 ASJ exome

AF:

0.00517

Gnomad4 EAS exome

AF:

0.0000791

Gnomad4 SAS exome

AF:

0.00268

Gnomad4 FIN exome

AF:

0.0192

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.00984

GnomAD4 genome

AF:

0.00938

AC:

1428

AN:

152236

Hom.:

Cov.:

AF XY:

0.00970

AC XY:

722

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00765

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.00794

AC:

960

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 05, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 23, 2015	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	ABCB6: BS1, BS2 -

Acute intermittent porphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Variegate porphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Protoporphyria, erythropoietic, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Hereditary coproporphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.020

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.75

D;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

D;D

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

0.77

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.3

D;.

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

D;D

Vest4

0.85

MVP

0.97

MPC

0.82

ClinPred

0.044

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.91

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over