rs10499593

Positions:

• chr7-36611060-G-A
• chr7-36611060-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001637.4(AOAH):​c.846+5320C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,236 control chromosomes in the GnomAD database, including 369 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 0.058 (369 hom., cov: 32)
• Consequence: AOAH NM_001637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

AOAH (HGNC:548): (acyloxyacyl hydrolase) This locus encodes both the light and heavy subunits of acyloxyacyl hydrolase. The encoded enzyme catalyzes the hydrolysis of acyloxylacyl-linked fatty acyl chains from bacterial lipopolysaccharides, effectively detoxifying these molecules. The encoded protein may play a role in modulating host inflammatory response to gram-negative bacteria. Alternatively spliced transcript variants have been described.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOAH	NM_001637.4	c.846+5320C>T		intron_variant		ENST00000617537.5	NP_001628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOAH	ENST00000617537.5	c.846+5320C>T		intron_variant		1	NM_001637.4	ENSP00000483783	P1
AOAH	ENST00000617267.4	c.846+5320C>T		intron_variant		1		ENSP00000479664
AOAH	ENST00000612871.4	c.750+5320C>T		intron_variant		2		ENSP00000484305

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8812 AN: 152118 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0579 AC: 8812 AN: 152236 Hom.: 369 Cov.: 32 AF XY: 0.0591 AC XY: 4398 AN XY: 74446

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0665 Hom.: 195

Bravo AF: 0.0629

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.034
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10499593; hg19: chr7-36650666;