rs2026015

Variant names:

• chr10-27230198-T-C
• rs2026015
• NM_145698.5:c.375+1550A>G

Variant summary

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

The NM_145698.5(ACBD5):​c.375+1550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 151,488 control chromosomes in the GnomAD database, including 39,748 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 0.72 (39748 hom., cov: 30)
• Consequence: ACBD5 NM_145698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.30
• Publications: 1 publications found

Genes affected

ACBD5 (HGNC:23338): (acyl-CoA binding domain containing 5) This gene encodes a member of the acyl-Coenzyme A binding protein family, known to function in the transport and distribution of long chain acyl-Coenzyme A in cells. This gene may play a role in the differentiation of megakaryocytes and formation of platelets. A related protein in yeast is involved in autophagy of peroxisomes. A mutation in this gene has been associated with autosomal dominant thrombocytopenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACBD5 Gene-Disease associations (from GenCC):

• retinal dystrophy with leukodystrophy

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• acyl-CoA binding domain containing protein 5 deficiency

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACBD5	NM_145698.5	c.375+1550A>G		intron_variant	Intron 4 of 12	ENST00000396271.8	NP_663736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACBD5	ENST00000396271.8	c.375+1550A>G		intron_variant	Intron 4 of 12	1	NM_145698.5	ENSP00000379568.3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109536 AN: 151372 Hom.: 39734 Cov.: 30

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.723 AC: 109579 AN: 151488 Hom.: 39748 Cov.: 30 AF XY: 0.724 AC XY: 53550 AN XY: 73964

African (AFR) AF: 0.705 AC: 29136 AN: 41344

American (AMR) AF: 0.732 AC: 11141 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2481 AN: 3464

East Asian (EAS) AF: 0.561 AC: 2891 AN: 5156

South Asian (SAS) AF: 0.681 AC: 3276 AN: 4810

European-Finnish (FIN) AF: 0.776 AC: 8019 AN: 10332

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.741 AC: 50285 AN: 67850

Other (OTH) AF: 0.698 AC: 1473 AN: 2110

Alfa AF: 0.741 Hom.: 16103

Bravo AF: 0.720

Asia WGS AF: 0.596 AC: 2055 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.079
DANN	Benign	0.73
PhyloP100		-4.3
Mutation Taster		=100/0	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: rs2026015; hg19: chr10-27519127;