NM_001163941.2:c.2421+2645C>A

Variant names:

• chr7-20707452-C-A
• rs10488577
• NM_001163941.2:c.2421+2645C>A

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+2645C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,178 control chromosomes in the GnomAD database, including 1,367 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 0.11 (1367 hom., cov: 33)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 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+2645C>A		intron	N/A	NP_001157413.1	Q2M3G0-4
	ABCB5	NM_178559.6		c.1086+2645C>A		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+2645C>A		intron	N/A	ENSP00000384881.2	Q2M3G0-4
	ABCB5	ENST00000258738.10	TSL:1	c.1086+2645C>A		intron	N/A	ENSP00000258738.6	Q2M3G0-1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17025 AN: 152060 Hom.: 1367 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.112 AC: 17022 AN: 152178 Hom.: 1367 Cov.: 33 AF XY: 0.117 AC XY: 8711 AN XY: 74406

African (AFR) AF: 0.0446 AC: 1854 AN: 41550

American (AMR) AF: 0.117 AC: 1784 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2122 AN: 5156

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1712 AN: 10576

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7666 AN: 67990

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.119 Hom.: 831

Bravo AF: 0.106

Asia WGS AF: 0.332 AC: 1148 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.46
PhyloP100		-0.29
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: rs10488577; hg19: chr7-20747075;