chr7-20658647-A-G

Position:

• chr7-20658647-A-G

Variant summary

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

The NM_001163941.2(ABCB5):​c.1678A>G​(p.Lys560Glu) variant causes a missense change. The variant allele was found at a frequency of 0.327 in 1,613,714 control chromosomes in the GnomAD database, including 89,405 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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 0.39 (12600 hom., cov: 32)
  • Exomes 𝑓: 0.32 (76805 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.85

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=2.501106E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1678A>G	p.Lys560Glu	missense_variant	14/28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.343A>G	p.Lys115Glu	missense_variant	5/19		NP_848654.3
ABCB5	NM_001163942.2	c.343A>G	p.Lys115Glu	missense_variant	5/6		NP_001157414.1
ABCB5	NM_001163993.3	c.343A>G	p.Lys115Glu	missense_variant	5/6		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1678A>G	p.Lys560Glu	missense_variant	14/28	1	NM_001163941.2	ENSP00000384881	P1
ABCB5	ENST00000258738.10	c.343A>G	p.Lys115Glu	missense_variant	5/19	1		ENSP00000258738
ABCB5	ENST00000443026.6	c.343A>G	p.Lys115Glu	missense_variant	5/6	1		ENSP00000406730
ABCB5	ENST00000406935.5	c.343A>G	p.Lys115Glu	missense_variant	5/6	2		ENSP00000383899

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59200 AN: 151976 Hom.: 12576 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.341

GnomAD3 exomes AF: 0.333 AC: 83580 AN: 251176 Hom.: 14802 AF XY: 0.330 AC XY: 44772 AN XY: 135764

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.193

Gnomad SAS exome AF: 0.339

Gnomad FIN exome AF: 0.376

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.319

GnomAD4 exome AF: 0.320 AC: 467897 AN: 1461620 Hom.: 76805 Cov.: 38 AF XY: 0.320 AC XY: 232709 AN XY: 727104

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.390 AC: 59277 AN: 152094 Hom.: 12600 Cov.: 32 AF XY: 0.389 AC XY: 28907 AN XY: 74344

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.341

Alfa AF: 0.325 Hom.: 21496

Bravo AF: 0.393

TwinsUK AF: 0.304 AC: 1126

ALSPAC AF: 0.306 AC: 1180

ESP6500AA AF: 0.558 AC: 2460

ESP6500EA AF: 0.319 AC: 2742

ExAC AF: 0.337 AC: 40874

Asia WGS AF: 0.282 AC: 982 AN: 3478

EpiCase AF: 0.317

EpiControl AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.19
DEOGEN2	Benign	0.063	T;.;.;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.66	T;T;T;T
MetaRNN	Benign	0.000025	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.3	.;N;N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	3.5	N;N;N;N
REVEL	Benign	0.29
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.083
MPC		0.0067
ClinPred		0.010	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2301641; hg19: chr7-20698270; COSMIC: COSV51712679;