rs2987452

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-27222652-A-C
• chr10-27222652-A-G
• chr10-27222652-A-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.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
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

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>G		intron	N/A	NP_663736.2
	ACBD5	NM_001352568.1		c.544+555T>G		intron	N/A	NP_001339497.1
	ACBD5	NM_001352569.1		c.523+555T>G		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>G		intron	N/A	ENSP00000379568.3
	ACBD5	ENST00000375901.5	TSL:1	c.163+686T>G		intron	N/A	ENSP00000365066.1
	ACBD5	ENST00000375888.5	TSL:5	c.517+555T>G		intron	N/A	ENSP00000365049.1

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

African (AFR) AF: 0.912 AC: 37852 AN: 41520

American (AMR) AF: 0.968 AC: 14808 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3262 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5159 AN: 5176

South Asian (SAS) AF: 0.961 AC: 4646 AN: 4834

European-Finnish (FIN) AF: 0.963 AC: 10209 AN: 10598

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.966 AC: 65689 AN: 68034

Other (OTH) AF: 0.957 AC: 2020 AN: 2110

Alfa AF: 0.953 Hom.: 3398

Bravo AF: 0.953

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.64
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: rs2987452; hg19: chr10-27511581;