chr7-20728331-G-A

Variant names:

• chr7-20728331-G-A
• rs17143304
• NM_001163941.2:c.2743G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163941.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	NM_001163941.2	MANE Select	c.2743G>A	p.Ala915Thr	missense	Exon 23 of 28	NP_001157413.1
	ABCB5	NM_178559.6		c.1408G>A	p.Ala470Thr	missense	Exon 14 of 19	NP_848654.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.2743G>A	p.Ala915Thr	missense	Exon 23 of 28	ENSP00000384881.2
	ABCB5	ENST00000258738.10	TSL:1	c.1408G>A	p.Ala470Thr	missense	Exon 14 of 19	ENSP00000258738.6
	ABCB5	ENST00000441315.1	TSL:2	n.244G>A		non_coding_transcript_exon	Exon 3 of 8	ENSP00000398692.1

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

GnomAD2 exomes AF: 0.0273 AC: 6864 AN: 251222 AF XY: 0.0242

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 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

African (AFR) AF: 0.203 AC: 6800 AN: 33456

American (AMR) AF: 0.0203 AC: 908 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 299 AN: 26124

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39688

South Asian (SAS) AF: 0.0291 AC: 2505 AN: 86224

European-Finnish (FIN) AF: 0.0252 AC: 1346 AN: 53408

Middle Eastern (MID) AF: 0.0397 AC: 229 AN: 5766

European-Non Finnish (NFE) AF: 0.00762 AC: 8475 AN: 1111868

Other (OTH) AF: 0.0242 AC: 1461 AN: 60384

GnomAD4 genome AF: 0.0657 AC: 9996 AN: 152242 Hom.: 851 Cov.: 34 AF XY: 0.0644 AC XY: 4795 AN XY: 74438

African (AFR) AF: 0.199 AC: 8277 AN: 41532

American (AMR) AF: 0.0324 AC: 495 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4826

European-Finnish (FIN) AF: 0.0256 AC: 271 AN: 10598

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00905 AC: 616 AN: 68034

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0245 Hom.: 1082

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 v4.9

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
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.3	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.80
Sift	Benign	0.041	D
Sift4G	Benign	0.066	T
Vest4		0.19
MPC		0.034
ClinPred		0.022	T
GERP RS		3.0
Varity_R		0.27
gMVP		0.39
Mutation Taster		=82/18	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17143304; hg19: chr7-20767954;