dbSNP rs60197951: ABCB5:p.Ile1093Thr (chr7-20745287-T-C) – 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.3278T>C(p.Ile1093Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00606 in 1,614,014 control chromosomes in the GnomAD database, including 179 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 0.018 ( 65 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 114 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.24

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=0.00996232).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2 link	c.3278T>C	p.Ile1093Thr	missense_variant	Exon 26 of 28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 link	c.1943T>C	p.Ile648Thr	missense_variant	Exon 17 of 19		NP_848654.3	Q2M3G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCB5	ENST00000404938.7 link	c.3278T>C	p.Ile1093Thr	missense_variant	Exon 26 of 28	1	NM_001163941.2	ENSP00000384881.2	Q2M3G0-4
ABCB5	ENST00000258738.10 link	c.1943T>C	p.Ile648Thr	missense_variant	Exon 17 of 19	1		ENSP00000258738.6	Q2M3G0-1
ABCB5	ENST00000441315.1 link	n.779T>C		non_coding_transcript_exon_variant	Exon 6 of 8	2		ENSP00000398692.1	H7C165

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2739

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0515

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00276

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.00837

AC:

2103

AN:

251280

Hom.:

AF XY:

0.00714

AC XY:

970

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0524

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0306

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00394

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.00482

AC:

7040

AN:

1461736

Hom.:

114

Cov.:

AF XY:

0.00475

AC XY:

3452

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0600

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.0309

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00243

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.0180

AC:

2746

AN:

152278

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1336

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0515

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00276

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.00735

Hom.:

Bravo

AF:

0.0215

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.0561

AC:

247

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00852

AC:

1035

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.46

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.28

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.40

Sift

Benign

0.060

T;T

Sift4G

Uncertain

0.030

D;D

Vest4

0.47

MVP

0.42

MPC

0.0071

ClinPred

0.068

GERP RS

0.31

Varity_R

0.16

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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