rs2106562

Positions:

• chr7-20615645-C-G
• chr7-20615645-C-T

Variant summary

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

The 7-20615645-C-G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 151,182 control chromosomes in the GnomAD database, including 44,413 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 0.76 (44347 hom., cov: 27)
  • Exomes 𝑓: 0.74 (66 hom.)
• Consequence: ABCB5 NM_001163941.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB5	NM_001163941.2			upstream_gene_variant		ENST00000404938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7			upstream_gene_variant		1	NM_001163941.2	P1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115103 AN: 150838 Hom.: 44299 Cov.: 27

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.739 AC: 167 AN: 226 Hom.: 66 Cov.: 0 AF XY: 0.713 AC XY: 127 AN XY: 178

Gnomad4 AFR exome AF: 0.900

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.763 AC: 115212 AN: 150956 Hom.: 44347 Cov.: 27 AF XY: 0.762 AC XY: 56095 AN XY: 73640

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.756

Alfa AF: 0.645 Hom.: 1816

Bravo AF: 0.778

Asia WGS AF: 0.759 AC: 2637 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.56
DANN	Benign	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: rs2106562; hg19: chr7-20655268;