7-20658647-A-G

Variant names:

• chr7-20658647-A-G
• rs2301641
• NM_001163941.2:c.1678A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K560Q) has been classified as Uncertain significance.

• 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
• Publications: 40 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=2.501106E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 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.1678A>G	p.Lys560Glu	missense	Exon 14 of 28	NP_001157413.1	Q2M3G0-4
	ABCB5	NM_178559.6		c.343A>G	p.Lys115Glu	missense	Exon 5 of 19	NP_848654.3
	ABCB5	NM_001163942.2		c.343A>G	p.Lys115Glu	missense	Exon 5 of 6	NP_001157414.1	Q2M3G0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.1678A>G	p.Lys560Glu	missense	Exon 14 of 28	ENSP00000384881.2	Q2M3G0-4
	ABCB5	ENST00000258738.10	TSL:1	c.343A>G	p.Lys115Glu	missense	Exon 5 of 19	ENSP00000258738.6	Q2M3G0-1
	ABCB5	ENST00000443026.6	TSL:1	c.343A>G	p.Lys115Glu	missense	Exon 5 of 6	ENSP00000406730.2	Q2M3G0-2

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

GnomAD2 exomes AF: 0.333 AC: 83580 AN: 251176 AF XY: 0.330

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 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

African (AFR) AF: 0.563 AC: 18839 AN: 33468

American (AMR) AF: 0.327 AC: 14621 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 8697 AN: 26130

East Asian (EAS) AF: 0.218 AC: 8633 AN: 39658

South Asian (SAS) AF: 0.341 AC: 29411 AN: 86248

European-Finnish (FIN) AF: 0.368 AC: 19647 AN: 53404

Middle Eastern (MID) AF: 0.284 AC: 1638 AN: 5768

European-Non Finnish (NFE) AF: 0.312 AC: 346625 AN: 1111870

Other (OTH) AF: 0.328 AC: 19786 AN: 60378

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

African (AFR) AF: 0.569 AC: 23592 AN: 41450

American (AMR) AF: 0.347 AC: 5298 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1104 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5180

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3934 AN: 10576

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21742 AN: 67992

Other (OTH) AF: 0.341 AC: 721 AN: 2116

Alfa AF: 0.332 Hom.: 42489

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 v4.9

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
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.3	N
PhyloP100		6.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.29
Sift	Benign	1.0	T
Sift4G	Benign	1.0	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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301641; hg19: chr7-20698270; COSMIC: COSV51712679;