7-20723023-G-T

Variant names:

• chr7-20723023-G-T
• rs62453384
• NM_001163941.2:c.2429G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163941.2(ABCB5):​c.2429G>T​(p.Gly810Val) variant causes a missense change. The variant allele was found at a frequency of 0.341 in 1,612,860 control chromosomes in the GnomAD database, including 98,556 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 0.28 (6869 hom., cov: 32)
  • Exomes 𝑓: 0.35 (91687 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44
• Publications: 24 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=0.0019625425).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 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.2429G>T	p.Gly810Val	missense	Exon 21 of 28	NP_001157413.1
	ABCB5	NM_178559.6		c.1094G>T	p.Gly365Val	missense	Exon 12 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.2429G>T	p.Gly810Val	missense	Exon 21 of 28	ENSP00000384881.2
	ABCB5	ENST00000258738.10	TSL:1	c.1094G>T	p.Gly365Val	missense	Exon 12 of 19	ENSP00000258738.6
	ABCB5	ENST00000441315.1	TSL:2	n.-71G>T		upstream_gene	N/A	ENSP00000398692.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42695 AN: 151864 Hom.: 6868 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.311

GnomAD2 exomes AF: 0.299 AC: 75053 AN: 251022 AF XY: 0.309

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.347 AC: 507217 AN: 1460878 Hom.: 91687 Cov.: 35 AF XY: 0.348 AC XY: 253241 AN XY: 726828

African (AFR) AF: 0.130 AC: 4344 AN: 33468

American (AMR) AF: 0.199 AC: 8899 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 10425 AN: 26118

East Asian (EAS) AF: 0.154 AC: 6098 AN: 39638

South Asian (SAS) AF: 0.331 AC: 28571 AN: 86224

European-Finnish (FIN) AF: 0.220 AC: 11766 AN: 53396

Middle Eastern (MID) AF: 0.374 AC: 2157 AN: 5764

European-Non Finnish (NFE) AF: 0.373 AC: 414940 AN: 1111194

Other (OTH) AF: 0.332 AC: 20017 AN: 60354

GnomAD4 genome AF: 0.281 AC: 42708 AN: 151982 Hom.: 6869 Cov.: 32 AF XY: 0.275 AC XY: 20469 AN XY: 74304

African (AFR) AF: 0.144 AC: 5968 AN: 41470

American (AMR) AF: 0.280 AC: 4279 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3470

East Asian (EAS) AF: 0.174 AC: 900 AN: 5164

South Asian (SAS) AF: 0.319 AC: 1534 AN: 4816

European-Finnish (FIN) AF: 0.201 AC: 2122 AN: 10536

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25308 AN: 67950

Other (OTH) AF: 0.314 AC: 661 AN: 2106

Alfa AF: 0.342 Hom.: 30653

Bravo AF: 0.276

TwinsUK AF: 0.368 AC: 1363

ALSPAC AF: 0.366 AC: 1412

ESP6500AA AF: 0.141 AC: 621

ESP6500EA AF: 0.380 AC: 3269

ExAC AF: 0.305 AC: 37014

Asia WGS AF: 0.243 AC: 850 AN: 3478

EpiCase AF: 0.378

EpiControl AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.5	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.4
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.25
MPC		0.031
ClinPred		0.049	T
GERP RS		3.8
Varity_R		0.88
gMVP		0.58
Mutation Taster		=71/29	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: rs62453384; hg19: chr7-20762646; COSMIC: COSV51703763; COSMIC: COSV51703763;