19-17309480-G-T

Variant names:

• chr19-17309480-G-T
• rs2303745
• ENST00000951444.1:c.-9+315C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000593489.1(ABHD8):​c.40+687C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 549,694 control chromosomes in the GnomAD database, including 183,097 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 0.84 (54421 hom., cov: 31)
  • Exomes 𝑓: 0.79 (128676 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593489.1. 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
	DDA1	NM_024050.6	MANE Select	c.-175G>T		upstream_gene	N/A	NP_076955.1	Q9BW61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD8	ENST00000951444.1		c.-9+315C>A		intron	N/A	ENSP00000621503.1
	ABHD8	ENST00000593489.1	TSL:4	c.40+687C>A		intron	N/A	ENSP00000468883.1	M0QX40
	DDA1	ENST00000359866.9	TSL:1 MANE Select	c.-175G>T		upstream_gene	N/A	ENSP00000352928.3	Q9BW61

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127286 AN: 151994 Hom.: 54368 Cov.: 31

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.807

GnomAD4 exome AF: 0.794 AC: 315830 AN: 397582 Hom.: 128676 Cov.: 5 AF XY: 0.791 AC XY: 166922 AN XY: 210932

African (AFR) AF: 0.947 AC: 9342 AN: 9866

American (AMR) AF: 0.674 AC: 9839 AN: 14590

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 9523 AN: 11904

East Asian (EAS) AF: 0.372 AC: 9373 AN: 25182

South Asian (SAS) AF: 0.747 AC: 28697 AN: 38432

European-Finnish (FIN) AF: 0.903 AC: 30996 AN: 34324

Middle Eastern (MID) AF: 0.735 AC: 1263 AN: 1718

European-Non Finnish (NFE) AF: 0.831 AC: 198807 AN: 239108

Other (OTH) AF: 0.801 AC: 17990 AN: 22458

GnomAD4 genome AF: 0.838 AC: 127402 AN: 152112 Hom.: 54421 Cov.: 31 AF XY: 0.832 AC XY: 61820 AN XY: 74328

African (AFR) AF: 0.947 AC: 39324 AN: 41518

American (AMR) AF: 0.707 AC: 10807 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2767 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2020 AN: 5164

South Asian (SAS) AF: 0.738 AC: 3550 AN: 4812

European-Finnish (FIN) AF: 0.911 AC: 9617 AN: 10560

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56717 AN: 67980

Other (OTH) AF: 0.810 AC: 1713 AN: 2114

Alfa AF: 0.814 Hom.: 27359

Bravo AF: 0.823

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.53
PhyloP100		-1.2
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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: rs2303745;

hg19: chr19-17420289;

COSMIC: COSV53113625;