rs17218839

Positions:

• chr7-20705795-G-A
• chr7-20705795-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163941.2(ABCB5):​c.2421+988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 150,608 control chromosomes in the GnomAD database, including 4,402 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 0.23 (4402 hom., cov: 32)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB5	NM_001163941.2	c.2421+988G>A		intron_variant		ENST00000404938.7
ABCB5	NM_178559.6	c.1086+988G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7	c.2421+988G>A		intron_variant		1	NM_001163941.2	P1
ABCB5	ENST00000258738.10	c.1086+988G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35056 AN: 150502 Hom.: 4401 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.233 AC: 35077 AN: 150608 Hom.: 4402 Cov.: 32 AF XY: 0.229 AC XY: 16814 AN XY: 73544

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0145

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.242

Alfa AF: 0.196 Hom.: 720

Bravo AF: 0.233

Asia WGS AF: 0.100 AC: 348 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.71

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: rs17218839; hg19: chr7-20745418; COSMIC: COSV51706737;