Genetic Variant ACBD4:c.-153+4G>T (chr17-45135596-G-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BA1

The ENST00000591859.5(ACBD4):c.-153+4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 154,056 control chromosomes in the GnomAD database, including 16,733 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16499 hom., cov: 34)

Exomes 𝑓: 0.44 ( 234 hom. )

Consequence

ACBD4
ENST00000591859.5 splice_region, intron

Scores

Splicing: ADA: 0.9739

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.406

Publications

21 publications found

Variant links:

Genes affected

ACBD4 (HGNC:23337): (acyl-CoA binding domain containing 4) This gene encodes a member of the acyl-coenzyme A binding domain containing protein family. All family members contain the conserved acyl-Coenzyme A binding domain, which binds acyl-CoA thiol esters. They are thought to play roles in acyl-CoA dependent lipid metabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACBD4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACBD4	NM_001135705.3 link	c.-395G>T		upstream_gene_variant		ENST00000321854.13	NP_001129177.1	Q8NC06-2A0A0S2Z5Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACBD4	ENST00000591859.5 link	c.-153+4G>T		splice_region_variant, intron_variant	Intron 2 of 11	1		ENSP00000465610.1		Q8NC06-3
ACBD4	ENST00000321854.13 link	c.-395G>T		upstream_gene_variant		1	NM_001135705.3	ENSP00000314440.8		Q8NC06-2

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70099

AN:

152038

Hom.:

16491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.442

AC:

839

AN:

1900

Hom.:

234

Cov.:

AF XY:

0.474

AC XY:

539

AN XY:

1138

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.266

AC:

AN:

274

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.111

AC:

AN:

South Asian (SAS)

AF:

0.552

AC:

233

AN:

422

European-Finnish (FIN)

AF:

0.294

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.460

AC:

483

AN:

1050

Other (OTH)

AF:

0.520

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.461

AC:

70130

AN:

152156

Hom.:

16499

Cov.:

AF XY:

0.457

AC XY:

33994

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.442

AC:

18334

AN:

41488

American (AMR)

AF:

0.402

AC:

6153

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

1592

AN:

3468

East Asian (EAS)

AF:

0.250

AC:

1294

AN:

5176

South Asian (SAS)

AF:

0.541

AC:

2607

AN:

4818

European-Finnish (FIN)

AF:

0.415

AC:

4403

AN:

10608

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34261

AN:

67988

Other (OTH)

AF:

0.451

AC:

952

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2005

4009

6014

8018

10023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.486

Hom.:

65140

Bravo

AF:

0.457

Asia WGS

AF:

0.381

AC:

1325

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.5

(source)

DANN

Benign

0.69

PhyloP100

-0.41

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Pathogenic

0.81

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over