rs17143304

chr7-20728331-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.066 (851 hom., cov: 34)
  • Exomes 𝑓: 0.015 (855 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67

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]

ACMG classification

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/exons	MANE	UniProt
ABCB5	NM_001163941.2	c.2743G>A	p.Ala915Thr	missense_variant	23/28	ENST00000404938.7
ABCB5	NM_178559.6	c.1408G>A	p.Ala470Thr	missense_variant	14/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7	c.2743G>A	p.Ala915Thr	missense_variant	23/28	1	NM_001163941.2	P1
ABCB5	ENST00000258738.10	c.1408G>A	p.Ala470Thr	missense_variant	14/19	1
ABCB5	ENST00000441315.1	c.244G>A	p.Ala82Thr	missense_variant, NMD_transcript_variant	3/8	2

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9967 AN: 152124 Hom.: 845 Cov.: 34

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

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.: 29 AF XY: 0.0150 AC XY: 10921 AN XY: 727140

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.: 34 AF XY: 0.0644 AC XY: 4795 AN XY: 74438

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: 19

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.197 AC: 868

ESP6500EA AF: 0.0100 AC: 86

ExAC AF: 0.0307 AC: 3725

Asia WGS AF: 0.0270 AC: 95 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	T
BayesDel_noAF	Benign	-0.090
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.3	T
MutationTaster	Benign	0.047	P;P
PrimateAI	Uncertain	0.53	T
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	T
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

Other links and lift over

dbSNP: rs17143304; hg19: chr7-20767954;