chr7-20645861-C-A

Variant names:

• chr7-20645861-C-A
• rs2074000
• NM_001163941.2:c.784C>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.784C>A​(p.Gln262Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,588 control chromosomes in the GnomAD database, including 7,768 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 0.044 (838 hom., cov: 33)
  • Exomes 𝑓: 0.033 (6930 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• 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=0.004671544).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.784C>A	p.Gln262Lys	missense_variant	Exon 8 of 28	ENST00000404938.7	NP_001157413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.784C>A	p.Gln262Lys	missense_variant	Exon 8 of 28	1	NM_001163941.2	ENSP00000384881.2

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6665 AN: 152112 Hom.: 834 Cov.: 33

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.0458

GnomAD2 exomes AF: 0.0927 AC: 23032 AN: 248356 AF XY: 0.0836

Gnomad AFR exome AF: 0.00603

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.0264

Gnomad EAS exome AF: 0.487

Gnomad FIN exome AF: 0.0870

Gnomad NFE exome AF: 0.00534

Gnomad OTH exome AF: 0.0629

GnomAD4 exome AF: 0.0328 AC: 48003 AN: 1461358 Hom.: 6930 Cov.: 30 AF XY: 0.0332 AC XY: 24168 AN XY: 726936

African (AFR) AF: 0.00427 AC: 143 AN: 33472

American (AMR) AF: 0.234 AC: 10434 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 700 AN: 26106

East Asian (EAS) AF: 0.480 AC: 19048 AN: 39676

South Asian (SAS) AF: 0.0877 AC: 7562 AN: 86188

European-Finnish (FIN) AF: 0.0820 AC: 4377 AN: 53402

Middle Eastern (MID) AF: 0.00694 AC: 40 AN: 5764

European-Non Finnish (NFE) AF: 0.00274 AC: 3046 AN: 1111714

Other (OTH) AF: 0.0440 AC: 2653 AN: 60360

GnomAD4 genome AF: 0.0439 AC: 6683 AN: 152230 Hom.: 838 Cov.: 33 AF XY: 0.0529 AC XY: 3935 AN XY: 74420

African (AFR) AF: 0.00705 AC: 293 AN: 41556

American (AMR) AF: 0.130 AC: 1982 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2405 AN: 5182

South Asian (SAS) AF: 0.113 AC: 544 AN: 4822

European-Finnish (FIN) AF: 0.0893 AC: 946 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00488 AC: 332 AN: 68008

Other (OTH) AF: 0.0463 AC: 98 AN: 2116

Alfa AF: 0.0274 Hom.: 2493

Bravo AF: 0.0511

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.00638 AC: 20

ESP6500EA AF: 0.00642 AC: 46

ExAC AF: 0.0831 AC: 10003

Asia WGS AF: 0.238 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.3	T
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Vest4		0.16
MPC		0.029
ClinPred		0.028	T
GERP RS		4.8
Varity_R		0.81
gMVP		0.57
Mutation Taster		=90/10	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: rs2074000; hg19: chr7-20685484; COSMIC: COSV51705853; COSMIC: COSV51705853;