Variant 7-20727129-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001163941.2(ABCB5):c.2715G>T(p.Gln905His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,612,608 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 81 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 85 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028603375).

BP6

Variant 7-20727129-G-T is Benign according to our data. Variant chr7-20727129-G-T is described in ClinVar as [Benign]. Clinvar id is 784107.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2 linkuse as main transcript	c.2715G>T	p.Gln905His	missense_variant	22/28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 linkuse as main transcript	c.1380G>T	p.Gln460His	missense_variant	13/19		NP_848654.3	Q2M3G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCB5	ENST00000404938.7 linkuse as main transcript	c.2715G>T	p.Gln905His	missense_variant	22/28	1	NM_001163941.2	ENSP00000384881.2	Q2M3G0-4
ABCB5	ENST00000258738.10 linkuse as main transcript	c.1380G>T	p.Gln460His	missense_variant	13/19	1		ENSP00000258738.6	Q2M3G0-1
ABCB5	ENST00000441315.1 linkuse as main transcript	n.216G>T		non_coding_transcript_exon_variant	2/8	2		ENSP00000398692.1	H7C165

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2741

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00603

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00487

AC:

1218

AN:

250122

Hom.:

AF XY:

0.00341

AC XY:

461

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.0682

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00184

AC:

2692

AN:

1460338

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1080

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.0671

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00428

GnomAD4 genome

AF:

0.0180

AC:

2748

AN:

152270

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1279

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0627

Gnomad4 AMR

AF:

0.00602

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00315

Hom.:

Bravo

AF:

0.0207

ESP6500AA

AF:

0.0613

AC:

270

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00575

AC:

698

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.077

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.8

.;L

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.20

Sift

Benign

0.14

T;T

Sift4G

Benign

0.12

T;T

Vest4

0.23

MutPred

0.41

.;Loss of MoRF binding (P = 0.1756);

MVP

0.40

MPC

0.0075

ClinPred

0.0058

GERP RS

1.6

Varity_R

0.13

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over