rs6461516

Positions:

• chr7-20739150-C-G
• chr7-20739150-C-T

Variant summary

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

The NM_001163941.2(ABCB5):​c.3024+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,582,688 control chromosomes in the GnomAD database, including 552,748 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 0.82 (51497 hom., cov: 30)
  • Exomes 𝑓: 0.84 (501251 hom.)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.3024+11C>G		intron_variant		ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.1689+11C>G		intron_variant			NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.3024+11C>G		intron_variant		1	NM_001163941.2	ENSP00000384881.2
ABCB5	ENST00000258738.10	c.1689+11C>G		intron_variant		1		ENSP00000258738.6
ABCB5	ENST00000441315.1	n.525+11C>G		intron_variant		2		ENSP00000398692.1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124833 AN: 151850 Hom.: 51455 Cov.: 30

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.847

GnomAD3 exomes AF: 0.830 AC: 177377 AN: 213794 Hom.: 73672 AF XY: 0.825 AC XY: 94889 AN XY: 114972

Gnomad AFR exome AF: 0.770

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.874

Gnomad EAS exome AF: 0.845

Gnomad SAS exome AF: 0.748

Gnomad FIN exome AF: 0.852

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.843

GnomAD4 exome AF: 0.836 AC: 1196686 AN: 1430720 Hom.: 501251 Cov.: 42 AF XY: 0.834 AC XY: 591416 AN XY: 709152

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.873

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.856

Gnomad4 NFE exome AF: 0.840

Gnomad4 OTH exome AF: 0.843

GnomAD4 genome AF: 0.822 AC: 124932 AN: 151968 Hom.: 51497 Cov.: 30 AF XY: 0.822 AC XY: 61058 AN XY: 74274

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.849

Alfa AF: 0.834 Hom.: 9826

Bravo AF: 0.824

Asia WGS AF: 0.816 AC: 2837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6461516; hg19: chr7-20778773; COSMIC: COSV51703212;