dbSNP rs17143304: ABCB5:p.Ala915Thr (chr7-20728331-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.2743G>A(p.Ala915Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,613,860 control chromosomes in the GnomAD database, including 1,706 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.066 ( 851 hom., cov: 34)

Exomes 𝑓: 0.015 ( 855 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.67

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=0.0018613935).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2 link	c.2743G>A	p.Ala915Thr	missense_variant	Exon 23 of 28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 link	c.1408G>A	p.Ala470Thr	missense_variant	Exon 14 of 19		NP_848654.3	Q2M3G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCB5	ENST00000404938.7 link	c.2743G>A	p.Ala915Thr	missense_variant	Exon 23 of 28	1	NM_001163941.2	ENSP00000384881.2	Q2M3G0-4
ABCB5	ENST00000258738.10 link	c.1408G>A	p.Ala470Thr	missense_variant	Exon 14 of 19	1		ENSP00000258738.6	Q2M3G0-1
ABCB5	ENST00000441315.1 link	n.244G>A		non_coding_transcript_exon_variant	Exon 3 of 8	2		ENSP00000398692.1	H7C165

Frequencies

GnomAD3 genomes

AF:

0.0655

AC:

9967

AN:

152124

Hom.:

845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00905

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0273

AC:

6864

AN:

251222

Hom.:

398

AF XY:

0.0242

AC XY:

3290

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0298

Gnomad FIN exome

AF:

0.0274

Gnomad NFE exome

AF:

0.00943

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0151

AC:

22027

AN:

1461618

Hom.:

855

Cov.:

AF XY:

0.0150

AC XY:

10921

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0291

Gnomad4 FIN exome

AF:

0.0252

Gnomad4 NFE exome

AF:

0.00762

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.0657

AC:

9996

AN:

152242

Hom.:

851

Cov.:

AF XY:

0.0644

AC XY:

4795

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0324

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0274

Gnomad4 FIN

AF:

0.0256

Gnomad4 NFE

AF:

0.00905

Gnomad4 OTH

AF:

0.0520

Alfa

AF:

0.0189

Hom.:

388

Bravo

AF:

0.0717

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.197

AC:

868

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.0307

AC:

3725

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.00966

EpiControl

AF:

0.0100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.3

MutationAssessor

Benign

1.9

.;L

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.5

D;D

REVEL

Pathogenic

0.80

Sift

Benign

0.041

D;T

Sift4G

Benign

0.066

T;T

Vest4

0.19

MPC

0.034

ClinPred

0.022

GERP RS

3.0

Varity_R

0.27

gMVP

0.39

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