rs2987452

chr10-27222652-A-Cchr10-27222652-A-Gchr10-27222652-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145698.5(ACBD5):c.490+686T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,240 control chromosomes in the GnomAD database, including 68,927 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 0.95 (68927 hom., cov: 31)
• Consequence: ACBD5 NM_145698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACBD5	NM_145698.5	c.490+686T>G		intron_variant		ENST00000396271.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACBD5	ENST00000396271.8	c.490+686T>G		intron_variant		1	NM_145698.5	P4

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144727 AN: 152122 Hom.: 68897 Cov.: 31

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.951 AC: 144811 AN: 152240 Hom.: 68927 Cov.: 31 AF XY: 0.952 AC XY: 70840 AN XY: 74436

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.968

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.961

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.957

Alfa AF: 0.956 Hom.: 3059

Bravo AF: 0.953

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2987452; hg19: chr10-27511581;