17-45135596-G-A

Variant names:

• chr17-45135596-G-A
• rs2291447
• ENST00000591859.5:c.-153+4G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001321352.2(ACBD4):​c.-153+4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: ACBD4 NM_001321352.2 splice_region, intron
• Scores: Splicing: ADA: 0.9645
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321352.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACBD4	NM_001378112.1		c.-700G>A		5_prime_UTR	Exon 2 of 10	NP_001365041.1
	ACBD4	NM_001321352.2		c.-153+4G>A		splice_region intron	N/A	NP_001308281.1	A0A0S2Z5Y4
	ACBD4	NM_001321353.2		c.-150+4G>A		splice_region intron	N/A	NP_001308282.1	Q8NC06-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACBD4	ENST00000591859.5	TSL:1	c.-153+4G>A		splice_region intron	N/A	ENSP00000465610.1	Q8NC06-3
	ACBD4	ENST00000431281.5	TSL:5	c.-150G>A		splice_region	Exon 2 of 12	ENSP00000405969.1	Q8NC06-3
	ACBD4	ENST00000865137.1		c.-150G>A		splice_region	Exon 1 of 11	ENSP00000535196.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		-0.41
PromoterAI		-0.0023	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.96
dbscSNV1_RF	Pathogenic	0.81

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2291447;

hg19: chr17-43212963;