chr10-27222652-A-T

Position:

• chr10-27222652-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACBD5	NM_145698.5	c.490+686T>A		intron_variant		ENST00000396271.8	NP_663736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACBD5	ENST00000396271.8	c.490+686T>A		intron_variant		1	NM_145698.5	ENSP00000379568	P4

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

Gnomad4 AFR AF: 0.000795

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00910

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00507

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00135 Hom.: 3059

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.54

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;