9-111578960-A-T

Variant names:

• chr9-111578960-A-T
• rs74633160
• NM_001146108.2:c.496-9T>A

Variant summary

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

The NM_001146108.2(PTGR1):​c.496-9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 303,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 26)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: PTGR1 NM_001146108.2 intron
• Scores: Splicing: ADA: 0.0002446
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

Genes affected

PTGR1 (HGNC:18429): (prostaglandin reductase 1) This gene encodes an enzyme that is involved in the inactivation of the chemotactic factor, leukotriene B4. The encoded protein specifically catalyzes the NADP+ dependent conversion of leukotriene B4 to 12-oxo-leukotriene B4. A pseudogene of this gene is found on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

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=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146108.2. 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
	PTGR1	NM_001146108.2	MANE Select	c.496-9T>A		intron	N/A	NP_001139580.1	Q14914-1
	PTGR1	NM_012212.3		c.496-9T>A		intron	N/A	NP_036344.2	Q14914-1
	PTGR1	NM_001146109.2		c.496-9T>A		intron	N/A	NP_001139581.1	Q14914-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGR1	ENST00000407693.7	TSL:1 MANE Select	c.496-9T>A		intron	N/A	ENSP00000385763.2	Q14914-1
	PTGR1	ENST00000309195.9	TSL:1	c.496-9T>A		intron	N/A	ENSP00000311572.5	Q14914-1
	PTGR1	ENST00000878676.1		c.496-9T>A		intron	N/A	ENSP00000548735.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000660 AC: 2 AN: 303170 Hom.: 0 Cov.: 0 AF XY: 0.00000666 AC XY: 1 AN XY: 150114

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3882

American (AMR) AF: 0.00 AC: 0 AN: 8486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3798

East Asian (EAS) AF: 0.00 AC: 0 AN: 12728

South Asian (SAS) AF: 0.00 AC: 0 AN: 20928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1370

European-Non Finnish (NFE) AF: 0.00000886 AC: 2 AN: 225804

Other (OTH) AF: 0.00 AC: 0 AN: 11892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.9
DANN	Benign	0.63
PhyloP100		1.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.19
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

Other links and lift over

dbSNP: rs74633160; hg19: chr9-114341240;