dbSNP rs34603556: ABCB5:p.Met1? (chr7-20651424-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PVS1_SupportingBA1

The NM_178559.6(ABCB5):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,613,604 control chromosomes in the GnomAD database, including 32,790 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 0.16 ( 2326 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30464 hom. )

Consequence

ABCB5
NM_178559.6 start_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.104

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 -7 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 49 codons. Genomic position: 20651567. Lost 0.059 part of the original CDS.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2 link	c.1337T>C	p.Met446Thr	missense_variant	Exon 13 of 28	ENST00000404938.7	NP_001157413.1	Q2M3G0-4
ABCB5	NM_178559.6 link	c.2T>C	p.Met1?	start_lost	Exon 4 of 19		NP_848654.3	Q2M3G0-1
ABCB5	NM_001163942.2 link	c.2T>C	p.Met1?	start_lost	Exon 4 of 6		NP_001157414.1	Q2M3G0-2A0A024RA03
ABCB5	NM_001163993.3 link	c.2T>C	p.Met1?	start_lost	Exon 4 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.1337T>C	p.Met446Thr	missense_variant	Exon 13 of 28	1	NM_001163941.2	ENSP00000384881.2		Q2M3G0-4

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23985

AN:

152028

Hom.:

2324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.178

AC:

44665

AN:

250788

Hom.:

4868

AF XY:

0.186

AC XY:

25271

AN XY:

135522

show subpopulations

Gnomad AFR exome

AF:

0.0527

Gnomad AMR exome

AF:

0.0868

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.0345

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.197

AC:

288465

AN:

1461458

Hom.:

30464

Cov.:

AF XY:

0.199

AC XY:

144719

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.0458

Gnomad4 AMR exome

AF:

0.0912

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.0225

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.158

AC:

23988

AN:

152146

Hom.:

2326

Cov.:

AF XY:

0.162

AC XY:

12034

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0549

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.0351

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.191

Hom.:

5536

Bravo

AF:

0.138

TwinsUK

AF:

0.213

AC:

791

ALSPAC

AF:

0.205

AC:

789

ESP6500AA

AF:

0.0601

AC:

265

ESP6500EA

AF:

0.203

AC:

1749

ExAC

AF:

0.180

AC:

21907

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

EpiCase

AF:

0.209

EpiControl

AF:

0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.94

DANN

Benign

0.68

DEOGEN2

Benign

0.089

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.060

T;D;D;D

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.36

PROVEAN

Benign

2.4

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

1.0

T;D;D;D

Sift4G

Benign

1.0

T;D;D;D

Polyphen

0.19

.;B;.;.

Vest4

0.096

MPC

0.0071

ClinPred

0.0025

GERP RS

0.38

Varity_R

0.039

gMVP

0.48

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