rs61227829

Positions:

• chr7-20651596-G-A
• chr7-20651596-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001163941.2(ABCB5):​c.1509G>A​(p.Ala503Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,814 control chromosomes in the GnomAD database, including 13,029 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 0.10 (949 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12080 hom.)
• Consequence: ABCB5 NM_001163941.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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]

ABCB5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=-0.291 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1509G>A	p.Ala503Ala	synonymous_variant	13/28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.174G>A	p.Ala58Ala	synonymous_variant	4/19		NP_848654.3
ABCB5	NM_001163942.2	c.174G>A	p.Ala58Ala	synonymous_variant	4/6		NP_001157414.1
ABCB5	NM_001163993.3	c.174G>A	p.Ala58Ala	synonymous_variant	4/6		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1509G>A	p.Ala503Ala	synonymous_variant	13/28	1	NM_001163941.2	ENSP00000384881.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15446 AN: 152052 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0915

GnomAD3 exomes AF: 0.104 AC: 26232 AN: 251112 Hom.: 1747 AF XY: 0.107 AC XY: 14475 AN XY: 135712

Gnomad AFR exome AF: 0.0387

Gnomad AMR exome AF: 0.0608

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.00120

Gnomad SAS exome AF: 0.0652

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.123 AC: 180319 AN: 1461644 Hom.: 12080 Cov.: 32 AF XY: 0.122 AC XY: 88761 AN XY: 727134

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.0635

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.000857

Gnomad4 SAS exome AF: 0.0659

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.102 AC: 15453 AN: 152170 Hom.: 949 Cov.: 32 AF XY: 0.103 AC XY: 7628 AN XY: 74384

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.0939

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.0905

Alfa AF: 0.126 Hom.: 1609

Bravo AF: 0.0914

Asia WGS AF: 0.0290 AC: 99 AN: 3478

EpiCase AF: 0.137

EpiControl AF: 0.130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.66

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: rs61227829; hg19: chr7-20691219;