rs788216

Variant names:

• chr10-27221405-T-A
• rs788216
• NM_145698.5:c.491-1548A>T

Variant summary

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

The NM_145698.5(ACBD5):​c.491-1548A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,200 control chromosomes in the GnomAD database, including 3,560 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 0.20 (3560 hom., cov: 31)
• Consequence: ACBD5 NM_145698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 3 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACBD5	NM_145698.5	c.491-1548A>T		intron_variant	Intron 5 of 12	ENST00000396271.8	NP_663736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACBD5	ENST00000396271.8	c.491-1548A>T		intron_variant	Intron 5 of 12	1	NM_145698.5	ENSP00000379568.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29679 AN: 152082 Hom.: 3548 Cov.: 31

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.195 AC: 29705 AN: 152200 Hom.: 3560 Cov.: 31 AF XY: 0.197 AC XY: 14624 AN XY: 74408

African (AFR) AF: 0.0509 AC: 2117 AN: 41568

American (AMR) AF: 0.235 AC: 3598 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1662 AN: 5162

South Asian (SAS) AF: 0.245 AC: 1184 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2268 AN: 10574

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17240 AN: 67988

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.216 Hom.: 530

Bravo AF: 0.189

Asia WGS AF: 0.306 AC: 1063 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		-0.18
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: rs788216; hg19: chr10-27510334;