rs61741891

chr7-20645856-G-Achr7-20645856-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001163941.2(ABCB5):c.779G>A(p.Arg260Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,613,690 control chromosomes in the GnomAD database, including 5 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.

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0096052885).
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB5	NM_001163941.2	c.779G>A	p.Arg260Lys	missense_variant	8/28	ENST00000404938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7	c.779G>A	p.Arg260Lys	missense_variant	8/28	1	NM_001163941.2	P1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 319 AN: 152180 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000459 AC: 114 AN: 248434 Hom.: 2 AF XY: 0.000326 AC XY: 44 AN XY: 134992

Gnomad AFR exome AF: 0.00668

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000185 AC: 270 AN: 1461392 Hom.: 2 Cov.: 30 AF XY: 0.000160 AC XY: 116 AN XY: 726952

Gnomad4 AFR exome AF: 0.00687

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.00213 AC: 325 AN: 152298 Hom.: 3 Cov.: 33 AF XY: 0.00209 AC XY: 156 AN XY: 74474

Gnomad4 AFR AF: 0.00760

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000333 Hom.: 1

Bravo AF: 0.00232

ESP6500AA AF: 0.00702 AC: 22

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000573 AC: 69

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.042
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.0096	T
MetaSVM	Uncertain	-0.28	T
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.060	N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Vest4		0.078
MVP		0.76
MPC		0.0078
ClinPred		0.034	T
GERP RS		4.8
Varity_R		0.32
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs61741891; hg19: chr7-20685479;