Genetic Variant ABCB5:p.Thr131Ile (chr7-20643261-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001163941.2(ABCB5):c.392C>T(p.Thr131Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0338 in 1,613,684 control chromosomes in the GnomAD database, including 1,312 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 0.041 ( 199 hom., cov: 33)

Exomes 𝑓: 0.033 ( 1113 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.82

Publications

17 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2 link	c.392C>T	p.Thr131Ile	missense_variant	Exon 6 of 28	ENST00000404938.7	NP_001157413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7 link	c.392C>T	p.Thr131Ile	missense_variant	Exon 6 of 28	1	NM_001163941.2	ENSP00000384881.2

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6313

AN:

152144

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0678

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.0911

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0275

Gnomad OTH

AF:

0.0244

GnomAD2 exomes

AF:

0.0390

AC:

9678

AN:

248226

AF XY:

0.0409

show subpopulations

Gnomad AFR exome

AF:

0.0715

Gnomad AMR exome

AF:

0.00971

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0167

Gnomad NFE exome

AF:

0.0283

Gnomad OTH exome

AF:

0.0273

GnomAD4 exome

AF:

0.0330

AC:

48217

AN:

1461422

Hom.:

1113

Cov.:

AF XY:

0.0344

AC XY:

24976

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.0764

AC:

2558

AN:

33480

American (AMR)

AF:

0.0101

AC:

451

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

300

AN:

26132

East Asian (EAS)

AF:

0.0930

AC:

3690

AN:

39676

South Asian (SAS)

AF:

0.0785

AC:

6768

AN:

86220

European-Finnish (FIN)

AF:

0.0182

AC:

970

AN:

53394

Middle Eastern (MID)

AF:

0.0355

AC:

205

AN:

5768

European-Non Finnish (NFE)

AF:

0.0281

AC:

31278

AN:

1111720

Other (OTH)

AF:

0.0331

AC:

1997

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2621

5242

7863

10484

13105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1292

2584

3876

5168

6460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0415

AC:

6317

AN:

152262

Hom.:

199

Cov.:

AF XY:

0.0421

AC XY:

3135

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0678

AC:

2815

AN:

41544

American (AMR)

AF:

0.0201

AC:

307

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.108

AC:

561

AN:

5182

South Asian (SAS)

AF:

0.0906

AC:

437

AN:

4824

European-Finnish (FIN)

AF:

0.0188

AC:

199

AN:

10612

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0274

AC:

1867

AN:

68024

Other (OTH)

AF:

0.0241

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

303

605

908

1210

1513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0324

Hom.:

337

Bravo

AF:

0.0409

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0267

AC:

103

ESP6500AA

AF:

0.0727

AC:

228

ESP6500EA

AF:

0.0274

AC:

196

ExAC

AF:

0.0416

AC:

5012

EpiCase

AF:

0.0269

EpiControl

AF:

0.0265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.94

PhyloP100

4.8

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Benign

0.081

Vest4

0.10

MPC

0.020

ClinPred

0.048

GERP RS

3.0

Varity_R

0.24

gMVP

0.55

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over