chr7-20753490-A-G

Variant names:

• chr7-20753490-A-G
• rs58795451
• NM_001163941.2:c.3560A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP4_Strong BA1

The NM_001163941.2(ABCB5):​c.3560A>G​(p.Asp1187Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0063 in 1,613,378 control chromosomes in the GnomAD database, including 496 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 0.032 (250 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (246 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.29
• Publications: 12 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 -11 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 8: BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when AlphaMissense, BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.0044091344).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	NM_001163941.2	MANE Select	c.3560A>G	p.Asp1187Gly	missense	Exon 27 of 28	NP_001157413.1	Q2M3G0-4
	ABCB5	NM_178559.6		c.2225A>G	p.Asp742Gly	missense	Exon 18 of 19	NP_848654.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.3560A>G	p.Asp1187Gly	missense	Exon 27 of 28	ENSP00000384881.2	Q2M3G0-4
	ABCB5	ENST00000258738.10	TSL:1	c.2225A>G	p.Asp742Gly	missense	Exon 18 of 19	ENSP00000258738.6	Q2M3G0-1
	ABCB5	ENST00000441315.1	TSL:2	n.930+8052A>G		intron	N/A	ENSP00000398692.1	H7C165

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4822 AN: 152208 Hom.: 248 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00881 AC: 2206 AN: 250454 AF XY: 0.00641

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00614

Gnomad ASJ exome AF: 0.00748

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000547

Gnomad OTH exome AF: 0.00443

GnomAD4 exome AF: 0.00365 AC: 5337 AN: 1461052 Hom.: 246 Cov.: 30 AF XY: 0.00313 AC XY: 2277 AN XY: 726776

African (AFR) AF: 0.115 AC: 3834 AN: 33422

American (AMR) AF: 0.00657 AC: 293 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00716 AC: 187 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86046

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53388

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5764

European-Non Finnish (NFE) AF: 0.000470 AC: 522 AN: 1111700

Other (OTH) AF: 0.00742 AC: 448 AN: 60356

GnomAD4 genome AF: 0.0317 AC: 4833 AN: 152326 Hom.: 250 Cov.: 33 AF XY: 0.0304 AC XY: 2264 AN XY: 74488

African (AFR) AF: 0.109 AC: 4521 AN: 41560

American (AMR) AF: 0.0127 AC: 195 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68040

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0107 Hom.: 262

Bravo AF: 0.0363

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.107 AC: 470

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.0106 AC: 1287

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000710

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		9.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.30
MPC		0.039
ClinPred		0.11	T
GERP RS		5.2
Varity_R		0.89
gMVP		0.74
Mutation Taster		=89/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs58795451; hg19: chr7-20793113; COSMIC: COSV51722288;