7-20752375-A-G

Variant names:

• chr7-20752375-A-G
• rs2108258
• NM_001163941.2:c.3430-985A>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.3430-985A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 152,314 control chromosomes in the GnomAD database, including 254 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 0.046 (254 hom., cov: 33)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.909
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.3430-985A>G		intron_variant	Intron 26 of 27	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.2095-985A>G		intron_variant	Intron 17 of 18		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.3430-985A>G		intron_variant	Intron 26 of 27	1	NM_001163941.2	ENSP00000384881.2
ABCB5	ENST00000258738.10	c.2095-985A>G		intron_variant	Intron 17 of 18	1		ENSP00000258738.6
ABCB5	ENST00000441315.1	n.930+6937A>G		intron_variant	Intron 6 of 7	2		ENSP00000398692.1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7020 AN: 152196 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0460 AC: 7014 AN: 152314 Hom.: 254 Cov.: 33 AF XY: 0.0431 AC XY: 3207 AN XY: 74484

African (AFR) AF: 0.0115 AC: 478 AN: 41576

American (AMR) AF: 0.0416 AC: 636 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4830

European-Finnish (FIN) AF: 0.0358 AC: 380 AN: 10606

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0742 AC: 5044 AN: 68022

Other (OTH) AF: 0.0501 AC: 106 AN: 2116

Alfa AF: 0.0621 Hom.: 639

Bravo AF: 0.0471

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.82
PhyloP100		-0.91
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: rs2108258; hg19: chr7-20791998;