rs59334881

Positions:

• chr7-20745379-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001163941.2(ABCB5):​c.3370G>A​(p.Glu1124Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,178 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (29 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (34 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.93

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008663893).
• BP6: Variant 7-20745379-G-A is Benign according to our data. Variant chr7-20745379-G-A is described in ClinVar as [Benign]. Clinvar id is 785211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1737/152304) while in subpopulation AFR AF= 0.0397 (1650/41564). AF 95% confidence interval is 0.0381. There are 29 homozygotes in gnomad4. There are 806 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.3370G>A	p.Glu1124Lys	missense_variant	26/28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.2035G>A	p.Glu679Lys	missense_variant	17/19		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.3370G>A	p.Glu1124Lys	missense_variant	26/28	1	NM_001163941.2	ENSP00000384881	P1
ABCB5	ENST00000258738.10	c.2035G>A	p.Glu679Lys	missense_variant	17/19	1		ENSP00000258738
ABCB5	ENST00000441315.1	c.871G>A	p.Glu291Lys	missense_variant, NMD_transcript_variant	6/8	2		ENSP00000398692

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1737 AN: 152186 Hom.: 29 Cov.: 33

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00297 AC: 747 AN: 251456 Hom.: 8 AF XY: 0.00207 AC XY: 281 AN XY: 135896

Gnomad AFR exome AF: 0.0399

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00121 AC: 1776 AN: 1461874 Hom.: 34 Cov.: 31 AF XY: 0.00104 AC XY: 757 AN XY: 727244

Gnomad4 AFR exome AF: 0.0427

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000710

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.0114 AC: 1737 AN: 152304 Hom.: 29 Cov.: 33 AF XY: 0.0108 AC XY: 806 AN XY: 74478

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00262 Hom.: 13

Bravo AF: 0.0133

ESP6500AA AF: 0.0336 AC: 148

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00351 AC: 426

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D
MetaRNN	Benign	0.0087	T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.3	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.64
Sift	Benign	0.049	D;D
Sift4G	Uncertain	0.052	T;D
Vest4		0.78
MVP		0.67
MPC		0.040
ClinPred		0.046	T
GERP RS		4.0
Varity_R		0.47
gMVP		0.68

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: rs59334881; hg19: chr7-20785002;