rs2026015

Positions:

• chr10-27230198-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACBD5	NM_145698.5	c.375+1550A>G		intron_variant		ENST00000396271.8	NP_663736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACBD5	ENST00000396271.8	c.375+1550A>G		intron_variant		1	NM_145698.5	ENSP00000379568	P4

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

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.698

Alfa AF: 0.742 Hom.: 12910

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2026015; hg19: chr10-27519127;