10-27222652-A-T

Variant names:

• chr10-27222652-A-T
• rs2987452
• NM_145698.5:c.490+686T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_145698.5(ACBD5):​c.490+686T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 152,250 control chromosomes in the GnomAD database, including 3 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 0.0036 (3 hom., cov: 31)
• Consequence: ACBD5 NM_145698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 0 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=-0.98).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00359 (546/152250) while in subpopulation SAS AF = 0.0091 (44/4834). AF 95% confidence interval is 0.00697. There are 3 homozygotes in GnomAd4. There are 265 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145698.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACBD5	NM_145698.5	MANE Select	c.490+686T>A		intron	N/A	NP_663736.2
	ACBD5	NM_001352568.1		c.544+555T>A		intron	N/A	NP_001339497.1
	ACBD5	NM_001352569.1		c.523+555T>A		intron	N/A	NP_001339498.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACBD5	ENST00000396271.8	TSL:1 MANE Select	c.490+686T>A		intron	N/A	ENSP00000379568.3
	ACBD5	ENST00000375901.5	TSL:1	c.163+686T>A		intron	N/A	ENSP00000365066.1
	ACBD5	ENST00000375888.5	TSL:5	c.517+555T>A		intron	N/A	ENSP00000365049.1

Frequencies

GnomAD3 genomes AF: 0.00359 AC: 546 AN: 152132 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00909

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.00623

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

GnomAD4 genome AF: 0.00359 AC: 546 AN: 152250 Hom.: 3 Cov.: 31 AF XY: 0.00356 AC XY: 265 AN XY: 74442

African (AFR) AF: 0.000795 AC: 33 AN: 41528

American (AMR) AF: 0.00484 AC: 74 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00910 AC: 44 AN: 4834

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00507 AC: 345 AN: 68034

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00121 Hom.: 3398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism

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: rs2987452; hg19: chr10-27511581;