Genetic Variant ABCB5:p.Gly810Val (chr7-20723023-G-T) – 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.2429G>T(p.Gly810Val) variant causes a missense change. The variant allele was found at a frequency of 0.341 in 1,612,860 control chromosomes in the GnomAD database, including 98,556 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6869 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91687 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.44

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=0.0019625425).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2 link	c.2429G>T	p.Gly810Val	missense_variant	Exon 21 of 28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 link	c.1094G>T	p.Gly365Val	missense_variant	Exon 12 of 19		NP_848654.3	Q2M3G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCB5	ENST00000404938.7 link	c.2429G>T	p.Gly810Val	missense_variant	Exon 21 of 28	1	NM_001163941.2	ENSP00000384881.2	Q2M3G0-4
ABCB5	ENST00000258738.10 link	c.1094G>T	p.Gly365Val	missense_variant	Exon 12 of 19	1		ENSP00000258738.6	Q2M3G0-1
ABCB5	ENST00000441315.1 link	n.-71G>T		upstream_gene_variant		2		ENSP00000398692.1	H7C165

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42695

AN:

151864

Hom.:

6868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.299

AC:

75053

AN:

251022

Hom.:

12393

AF XY:

0.309

AC XY:

41898

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.347

AC:

507217

AN:

1460878

Hom.:

91687

Cov.:

AF XY:

0.348

AC XY:

253241

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.399

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.281

AC:

42708

AN:

151982

Hom.:

6869

Cov.:

AF XY:

0.275

AC XY:

20469

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.280

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.346

Hom.:

14919

Bravo

AF:

0.276

TwinsUK

AF:

0.368

AC:

1363

ALSPAC

AF:

0.366

AC:

1412

ESP6500AA

AF:

0.141

AC:

621

ESP6500EA

AF:

0.380

AC:

3269

ExAC

AF:

0.305

AC:

37014

Asia WGS

AF:

0.243

AC:

850

AN:

3478

EpiCase

AF:

0.378

EpiControl

AF:

0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.5

MutationAssessor

Pathogenic

3.2

.;M

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-8.3

D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Vest4

0.25

MPC

0.031

ClinPred

0.049

GERP RS

3.8

Varity_R

0.88

gMVP

0.58

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.

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