Genetic Variant ABCB5:p.Asp370Gly (chr7-20647981-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001163941.2(ABCB5):c.1109A>G(p.Asp370Gly) variant causes a missense change. The variant allele was found at a frequency of 0.119 in 1,598,770 control chromosomes in the GnomAD database, including 12,606 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 0.097 ( 921 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11685 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.94

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002119571).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2 link	c.1109A>G	p.Asp370Gly	missense_variant	Exon 11 of 28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 link	c.-227A>G		5_prime_UTR_variant	Exon 2 of 19		NP_848654.3	Q2M3G0-1
ABCB5	NM_001163942.2 link	c.-227A>G		5_prime_UTR_variant	Exon 2 of 6		NP_001157414.1	Q2M3G0-2A0A024RA03
ABCB5	NM_001163993.3 link	c.-227A>G		5_prime_UTR_variant	Exon 2 of 6		NP_001157465.1	Q2M3G0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7 link	c.1109A>G	p.Asp370Gly	missense_variant	Exon 11 of 28	1	NM_001163941.2	ENSP00000384881.2		Q2M3G0-4

Frequencies

GnomAD3 genomes

AF:

0.0974

AC:

14819

AN:

152146

Hom.:

921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.0931

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0573

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.0865

GnomAD2 exomes

AF:

0.103

AC:

25514

AN:

246530

AF XY:

0.106

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.0601

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.121

AC:

175034

AN:

1446506

Hom.:

11685

Cov.:

AF XY:

0.120

AC XY:

86476

AN XY:

720470

show subpopulations

African (AFR)

AF:

0.0211

AC:

700

AN:

33202

American (AMR)

AF:

0.0624

AC:

2770

AN:

44400

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

3127

AN:

26018

East Asian (EAS)

AF:

0.000808

AC:

AN:

39594

South Asian (SAS)

AF:

0.0657

AC:

5637

AN:

85826

European-Finnish (FIN)

AF:

0.192

AC:

10227

AN:

53344

Middle Eastern (MID)

AF:

0.102

AC:

580

AN:

5708

European-Non Finnish (NFE)

AF:

0.132

AC:

145293

AN:

1098574

Other (OTH)

AF:

0.111

AC:

6668

AN:

59840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

6526

13052

19577

26103

32629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5004

10008

15012

20016

25020

<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:

0.0973

AC:

14820

AN:

152264

Hom.:

921

Cov.:

AF XY:

0.0986

AC XY:

7342

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0269

AC:

1120

AN:

41576

American (AMR)

AF:

0.0930

AC:

1421

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

405

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.0578

AC:

279

AN:

4830

European-Finnish (FIN)

AF:

0.198

AC:

2102

AN:

10596

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9140

AN:

68000

Other (OTH)

AF:

0.0856

AC:

181

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

678

1356

2034

2712

3390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.118

Hom.:

3125

Bravo

AF:

0.0866

TwinsUK

AF:

0.140

AC:

519

ALSPAC

AF:

0.136

AC:

526

ESP6500AA

AF:

0.0284

AC:

ESP6500EA

AF:

0.134

AC:

962

ExAC

AF:

0.103

AC:

12379

Asia WGS

AF:

0.0270

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.82

PhyloP100

6.9

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.9

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Vest4

0.12

MPC

0.0095

ClinPred

0.063

GERP RS

4.2

Varity_R

0.56

gMVP

0.69

Mutation Taster

=192/108

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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