rs61227829

Variant names:

• chr7-20651596-G-A
• rs61227829
• NM_001163941.2:c.1509G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-20651596-G-A
• chr7-20651596-G-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.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
• Publications: 10 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=-0.3).
• 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 rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1509G>A	p.Ala503Ala	synonymous_variant	Exon 13 of 28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.174G>A	p.Ala58Ala	synonymous_variant	Exon 4 of 19		NP_848654.3
ABCB5	NM_001163942.2	c.174G>A	p.Ala58Ala	synonymous_variant	Exon 4 of 6		NP_001157414.1
ABCB5	NM_001163993.3	c.174G>A	p.Ala58Ala	synonymous_variant	Exon 4 of 6		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1509G>A	p.Ala503Ala	synonymous_variant	Exon 13 of 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

GnomAD2 exomes AF: 0.104 AC: 26232 AN: 251112 AF XY: 0.107

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 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

African (AFR) AF: 0.0365 AC: 1222 AN: 33470

American (AMR) AF: 0.0635 AC: 2837 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3160 AN: 26134

East Asian (EAS) AF: 0.000857 AC: 34 AN: 39678

South Asian (SAS) AF: 0.0659 AC: 5687 AN: 86256

European-Finnish (FIN) AF: 0.192 AC: 10245 AN: 53414

Middle Eastern (MID) AF: 0.104 AC: 602 AN: 5764

European-Non Finnish (NFE) AF: 0.135 AC: 149655 AN: 1111832

Other (OTH) AF: 0.114 AC: 6877 AN: 60390

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

African (AFR) AF: 0.0420 AC: 1743 AN: 41534

American (AMR) AF: 0.0939 AC: 1436 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3466

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0570 AC: 274 AN: 4810

European-Finnish (FIN) AF: 0.198 AC: 2096 AN: 10574

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9135 AN: 67998

Other (OTH) AF: 0.0905 AC: 191 AN: 2110

Alfa AF: 0.120 Hom.: 2080

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
PhyloP100		-0.29
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61227829; hg19: chr7-20691219; COSMIC: COSV108051726;