rs2893006

Variant names:

• chr7-20647558-C-T
• rs2893006
• NM_001163941.2:c.1005C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001163941.2(ABCB5):​c.1005C>T​(p.Ser335Ser) 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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1005C>T	p.Ser335Ser	synonymous_variant	Exon 10 of 28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.-331C>T		5_prime_UTR_variant	Exon 1 of 19		NP_848654.3
ABCB5	NM_001163942.2	c.-331C>T		5_prime_UTR_variant	Exon 1 of 6		NP_001157414.1
ABCB5	NM_001163993.3	c.-331C>T		5_prime_UTR_variant	Exon 1 of 6		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1005C>T	p.Ser335Ser	synonymous_variant	Exon 10 of 28	1	NM_001163941.2	ENSP00000384881.2

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

GnomAD2 exomes AF: 0.206 AC: 42114 AN: 204702 AF XY: 0.207

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 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

African (AFR) AF: 0.390 AC: 12802 AN: 32796

American (AMR) AF: 0.156 AC: 6185 AN: 39768

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5724 AN: 25536

East Asian (EAS) AF: 0.0231 AC: 900 AN: 39014

South Asian (SAS) AF: 0.253 AC: 20589 AN: 81324

European-Finnish (FIN) AF: 0.296 AC: 15236 AN: 51558

Middle Eastern (MID) AF: 0.188 AC: 1076 AN: 5710

European-Non Finnish (NFE) AF: 0.206 AC: 225802 AN: 1094770

Other (OTH) AF: 0.215 AC: 12721 AN: 59162

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

African (AFR) AF: 0.391 AC: 16204 AN: 41420

American (AMR) AF: 0.201 AC: 3065 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3472

East Asian (EAS) AF: 0.0365 AC: 189 AN: 5182

South Asian (SAS) AF: 0.244 AC: 1173 AN: 4810

European-Finnish (FIN) AF: 0.305 AC: 3217 AN: 10552

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14280 AN: 67976

Other (OTH) AF: 0.232 AC: 488 AN: 2102

Alfa AF: 0.225 Hom.: 14944

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
PhyloP100		0.012
PromoterAI		-0.033	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2893006; hg19: chr7-20687181; COSMIC: COSV108051725;