dbSNP rs6461515: ABCB5:p.Glu970Lys (chr7-20739023-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001163941.2(ABCB5):c.2908G>A(p.Glu970Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,611,028 control chromosomes in the GnomAD database, including 541,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.78 ( 46867 hom., cov: 32)

Exomes 𝑓: 0.82 ( 494329 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

ABCB5 (HGNC:46): (ATP binding cassette subfamily B member 5) ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005 [PubMed 15760339]).[supplied by OMIM, Mar 2008]

ABCB5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.054558E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2 link	c.2908G>A	p.Glu970Lys	missense_variant	Exon 24 of 28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 link	c.1573G>A	p.Glu525Lys	missense_variant	Exon 15 of 19		NP_848654.3	Q2M3G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCB5	ENST00000404938.7 link	c.2908G>A	p.Glu970Lys	missense_variant	Exon 24 of 28	1	NM_001163941.2	ENSP00000384881.2	Q2M3G0-4
ABCB5	ENST00000258738.10 link	c.1573G>A	p.Glu525Lys	missense_variant	Exon 15 of 19	1		ENSP00000258738.6	Q2M3G0-1
ABCB5	ENST00000441315.1 link	n.409G>A		non_coding_transcript_exon_variant	Exon 4 of 8	2		ENSP00000398692.1	H7C165

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118647

AN:

152000

Hom.:

46836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.846

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.800

GnomAD3 exomes

AF:

0.808

AC:

200324

AN:

247994

Hom.:

81320

AF XY:

0.806

AC XY:

107983

AN XY:

134054

show subpopulations

Gnomad AFR exome

AF:

0.659

Gnomad AMR exome

AF:

0.843

Gnomad ASJ exome

AF:

0.810

Gnomad EAS exome

AF:

0.818

Gnomad SAS exome

AF:

0.733

Gnomad FIN exome

AF:

0.854

Gnomad NFE exome

AF:

0.827

Gnomad OTH exome

AF:

0.816

GnomAD4 exome

AF:

0.822

AC:

1199296

AN:

1458910

Hom.:

494329

Cov.:

AF XY:

0.820

AC XY:

594753

AN XY:

725660

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.842

Gnomad4 ASJ exome

AF:

0.808

Gnomad4 EAS exome

AF:

0.855

Gnomad4 SAS exome

AF:

0.732

Gnomad4 FIN exome

AF:

0.856

Gnomad4 NFE exome

AF:

0.831

Gnomad4 OTH exome

AF:

0.817

GnomAD4 genome

AF:

0.780

AC:

118728

AN:

152118

Hom.:

46867

Cov.:

AF XY:

0.780

AC XY:

58036

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.664

Gnomad4 AMR

AF:

0.812

Gnomad4 ASJ

AF:

0.814

Gnomad4 EAS

AF:

0.833

Gnomad4 SAS

AF:

0.722

Gnomad4 FIN

AF:

0.846

Gnomad4 NFE

AF:

0.831

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.819

Hom.:

125982

Bravo

AF:

0.776

TwinsUK

AF:

0.821

AC:

3043

ALSPAC

AF:

0.821

AC:

3163

ESP6500AA

AF:

0.666

AC:

2933

ESP6500EA

AF:

0.829

AC:

7131

ExAC

AF:

0.802

AC:

97349

Asia WGS

AF:

0.792

AC:

2755

AN:

3478

EpiCase

AF:

0.830

EpiControl

AF:

0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

9.1e-7

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

.;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.20

Sift

Benign

0.10

T;T

Sift4G

Benign

0.27

T;T

Vest4

0.17

MPC

0.012

ClinPred

0.0098

GERP RS

4.1

Varity_R

0.11

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over