19-17309480-G-A

Variant names:

• chr19-17309480-G-A
• rs2303745
• ENST00000593489.1:c.40+687C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000593489.1(ABHD8):​c.40+687C>T variant causes a 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABHD8 ENST00000593489.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 25 publications found

Genes affected

ABHD8 (HGNC:23759): (abhydrolase domain containing 8) This gene is upstream of, and in a head-to-head orientation with the gene for the mitochondrial ribosomal protein L34. The predicted protein contains alpha/beta hydrolase fold and secretory lipase domains. [provided by RefSeq, Jul 2008]

DDA1 (HGNC:28360): (DET1 and DDB1 associated 1) Involved in protein polyubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDA1	NM_024050.6	c.-175G>A		upstream_gene_variant		ENST00000359866.9	NP_076955.1
DDA1	XR_007067003.1	n.-83G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDA1	ENST00000359866.9	c.-175G>A		upstream_gene_variant		1	NM_024050.6	ENSP00000352928.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 397954 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 211132

African (AFR) AF: 0.00 AC: 0 AN: 9868

American (AMR) AF: 0.00 AC: 0 AN: 14622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11912

East Asian (EAS) AF: 0.00 AC: 0 AN: 25190

South Asian (SAS) AF: 0.00 AC: 0 AN: 38492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 239316

Other (OTH) AF: 0.00 AC: 0 AN: 22484

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 27359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.93
PhyloP100		-1.2
PromoterAI		-0.030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2303745; hg19: chr19-17420289;