Variant rs76179099 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001163941.2(ABCB5):c.1876A>T(p.Lys626*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,603,680 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0072 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 10 hom. )

Consequence

ABCB5
NM_001163941.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00715 (1089/152272) while in subpopulation AFR AF= 0.0252 (1045/41546). AF 95% confidence interval is 0.0239. There are 7 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2 linkuse as main transcript	c.1876A>T	p.Lys626*	stop_gained	16/28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 linkuse as main transcript	c.541A>T	p.Lys181*	stop_gained	7/19		NP_848654.3	Q2M3G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7 linkuse as main transcript	c.1876A>T	p.Lys626*	stop_gained	16/28	1	NM_001163941.2	ENSP00000384881.2		Q2M3G0-4
ABCB5	ENST00000258738.10 linkuse as main transcript	c.541A>T	p.Lys181*	stop_gained	7/19	1		ENSP00000258738.6		Q2M3G0-1

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1089

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00187

AC:

454

AN:

243024

Hom.:

AF XY:

0.00127

AC XY:

166

AN XY:

131152

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000356

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000697

AC:

1012

AN:

1451408

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

398

AN XY:

721976

show subpopulations

Gnomad4 AFR exome

AF:

0.0263

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000357

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000813

Gnomad4 OTH exome

AF:

0.00140

GnomAD4 genome

AF:

0.00715

AC:

1089

AN:

152272

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

511

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00785

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00229

AC:

278

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.097

FATHMM_MKL

Benign

0.52

Vest4

0.72

GERP RS

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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