rs2108259

Variant names:

• chr7-20706133-A-G
• rs2108259
• NM_001163941.2:c.2421+1326A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163941.2(ABCB5):​c.2421+1326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,086 control chromosomes in the GnomAD database, including 4,576 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 0.24 (4576 hom., cov: 32)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163941.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	NM_001163941.2	MANE Select	c.2421+1326A>G		intron	N/A	NP_001157413.1	Q2M3G0-4
	ABCB5	NM_178559.6		c.1086+1326A>G		intron	N/A	NP_848654.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.2421+1326A>G		intron	N/A	ENSP00000384881.2	Q2M3G0-4
	ABCB5	ENST00000258738.10	TSL:1	c.1086+1326A>G		intron	N/A	ENSP00000258738.6	Q2M3G0-1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35845 AN: 151968 Hom.: 4575 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.236 AC: 35864 AN: 152086 Hom.: 4576 Cov.: 32 AF XY: 0.231 AC XY: 17198 AN XY: 74344

African (AFR) AF: 0.196 AC: 8144 AN: 41486

American (AMR) AF: 0.250 AC: 3817 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3470

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5184

South Asian (SAS) AF: 0.168 AC: 814 AN: 4834

European-Finnish (FIN) AF: 0.208 AC: 2197 AN: 10566

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19070 AN: 67950

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.255 Hom.: 668

Bravo AF: 0.238

Asia WGS AF: 0.106 AC: 371 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.55
PhyloP100		0.31
Mutation Taster		=100/0	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: rs2108259; hg19: chr7-20745756;