rs2188594

Variant names:

• chr7-20639663-G-A
• rs2188594
• NM_001163941.2:c.315-3521G>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.315-3521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,068 control chromosomes in the GnomAD database, including 7,261 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 0.27 (7261 hom., cov: 33)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 6 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 (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	NM_001163941.2	MANE Select	c.315-3521G>A		intron	N/A	NP_001157413.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.315-3521G>A		intron	N/A	ENSP00000384881.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41187 AN: 151950 Hom.: 7248 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41246 AN: 152068 Hom.: 7261 Cov.: 33 AF XY: 0.269 AC XY: 20006 AN XY: 74334

African (AFR) AF: 0.500 AC: 20719 AN: 41478

American (AMR) AF: 0.233 AC: 3561 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5172

South Asian (SAS) AF: 0.263 AC: 1270 AN: 4822

European-Finnish (FIN) AF: 0.168 AC: 1773 AN: 10564

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11669 AN: 67966

Other (OTH) AF: 0.234 AC: 494 AN: 2110

Alfa AF: 0.190 Hom.: 5446

Bravo AF: 0.284

Asia WGS AF: 0.249 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.41
PhyloP100		0.11
Mutation Taster		=100/0	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: rs2188594; hg19: chr7-20679286;