Variant rs2301641 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001163941.2(ABCB5):c.1678A>G(p.Lys560Glu) variant causes a missense change. The variant allele was found at a frequency of 0.327 in 1,613,714 control chromosomes in the GnomAD database, including 89,405 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 same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K560Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.39 ( 12600 hom., cov: 32)

Exomes 𝑓: 0.32 ( 76805 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.501106E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCB5	NM_001163941.2 linkuse as main transcript	c.1678A>G	p.Lys560Glu	missense_variant	14/28	ENST00000404938.7
ABCB5	NM_178559.6 linkuse as main transcript	c.343A>G	p.Lys115Glu	missense_variant	5/19
ABCB5	NM_001163942.2 linkuse as main transcript	c.343A>G	p.Lys115Glu	missense_variant	5/6
ABCB5	NM_001163993.3 linkuse as main transcript	c.343A>G	p.Lys115Glu	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7 linkuse as main transcript	c.1678A>G	p.Lys560Glu	missense_variant	14/28	1	NM_001163941.2	P1	Q2M3G0-4
ABCB5	ENST00000258738.10 linkuse as main transcript	c.343A>G	p.Lys115Glu	missense_variant	5/19	1			Q2M3G0-1
ABCB5	ENST00000443026.6 linkuse as main transcript	c.343A>G	p.Lys115Glu	missense_variant	5/6	1			Q2M3G0-2
ABCB5	ENST00000406935.5 linkuse as main transcript	c.343A>G	p.Lys115Glu	missense_variant	5/6	2			Q2M3G0-3

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59200

AN:

151976

Hom.:

12576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.341

GnomAD3 exomes

AF:

0.333

AC:

83580

AN:

251176

Hom.:

14802

AF XY:

0.330

AC XY:

44772

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.376

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.320

AC:

467897

AN:

1461620

Hom.:

76805

Cov.:

AF XY:

0.320

AC XY:

232709

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.563

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.390

AC:

59277

AN:

152094

Hom.:

12600

Cov.:

AF XY:

0.389

AC XY:

28907

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.569

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.318

Gnomad4 EAS

AF:

0.202

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.341

Alfa

AF:

0.325

Hom.:

21496

Bravo

AF:

0.393

TwinsUK

AF:

0.304

AC:

1126

ALSPAC

AF:

0.306

AC:

1180

ESP6500AA

AF:

0.558

AC:

2460

ESP6500EA

AF:

0.319

AC:

2742

ExAC

AF:

0.337

AC:

40874

Asia WGS

AF:

0.282

AC:

982

AN:

3478

EpiCase

AF:

0.317

EpiControl

AF:

0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.19

DEOGEN2

Benign

0.063

T;.;.;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.66

T;T;T;T

MetaRNN

Benign

0.000025

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.3

.;N;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

3.5

N;N;N;N

REVEL

Benign

0.29

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.083

MPC

0.0067

ClinPred

0.010

GERP RS

4.7

Varity_R

0.12

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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