rs2893006

Positions:

• chr7-20647558-C-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.1005C>T​(p.Ser335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,581,616 control chromosomes in the GnomAD database, including 39,506 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 0.26 (5761 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33745 hom.)
• Consequence: ABCB5 NM_001163941.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.012 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1005C>T	p.Ser335=	synonymous_variant	10/28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_001163942.2	c.-331C>T		5_prime_UTR_variant	1/6		NP_001157414.1
ABCB5	NM_001163993.3	c.-331C>T		5_prime_UTR_variant	1/6		NP_001157465.1
ABCB5	NM_178559.6	c.-331C>T		5_prime_UTR_variant	1/19		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1005C>T	p.Ser335=	synonymous_variant	10/28	1	NM_001163941.2	ENSP00000384881	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39568 AN: 151860 Hom.: 5746 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.206 AC: 42114 AN: 204702 Hom.: 5049 AF XY: 0.207 AC XY: 22763 AN XY: 109798

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.0341

Gnomad SAS exome AF: 0.245

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.211 AC: 301035 AN: 1429638 Hom.: 33745 Cov.: 33 AF XY: 0.212 AC XY: 149789 AN XY: 708146

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.0231

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.261 AC: 39615 AN: 151978 Hom.: 5761 Cov.: 32 AF XY: 0.262 AC XY: 19485 AN XY: 74270

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0365

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.232

Alfa AF: 0.216 Hom.: 8950

Bravo AF: 0.257

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.5
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2893006; hg19: chr7-20687181;