chr17-45135596-G-T

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

2
Splicing: ADA: 0.9739
2

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]

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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
ACBD4NM_001135705.3 linkc.-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
ACBD4ENST00000591859.5 linkc.-153+4G>T splice_region_variant, intron_variant Intron 2 of 11 1 ENSP00000465610.1 Q8NC06-3
ACBD4ENST00000321854.13 linkc.-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.:
34
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.:
0
AF XY:
0.474
AC XY:
539
AN XY:
1138
show subpopulations
African (AFR)
AF:
0.500
AC:
5
AN:
10
American (AMR)
AF:
0.266
AC:
73
AN:
274
Ashkenazi Jewish (ASJ)
AF:
0.500
AC:
3
AN:
6
East Asian (EAS)
AF:
0.111
AC:
6
AN:
54
South Asian (SAS)
AF:
0.552
AC:
233
AN:
422
European-Finnish (FIN)
AF:
0.294
AC:
10
AN:
34
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.460
AC:
483
AN:
1050
Other (OTH)
AF:
0.520
AC:
26
AN:
50
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
22
43
65
86
108
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<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.:
34
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
0
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
0
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
DANN
Benign
0.69
PhyloP100
-0.41
PromoterAI
0.018
Neutral
Mutation Taster
=300/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291447; hg19: chr17-43212963; API