9-111578960-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146108.2(PTGR1):c.496-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 436,868 control chromosomes in the GnomAD database, including 774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (411 hom., cov: 26)
  • Exomes 𝑓: 0.25 (363 hom.)
• Consequence: PTGR1 NM_001146108.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001471
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-111578960-A-G is Benign according to our data. Variant chr9-111578960-A-G is described in ClinVar as [Benign]. Clinvar id is 769755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGR1	NM_001146108.2	c.496-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000407693.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGR1	ENST00000407693.7	c.496-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001146108.2	P1

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 9514 AN: 138184 Hom.: 409 Cov.: 26

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0710

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0757

GnomAD4 exome AF: 0.252 AC: 75405 AN: 298660 Hom.: 363 Cov.: 0 AF XY: 0.257 AC XY: 37993 AN XY: 147928

Gnomad4 AFR exome AF: 0.0640

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.409

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.0690 AC: 9531 AN: 138208 Hom.: 411 Cov.: 26 AF XY: 0.0739 AC XY: 4921 AN XY: 66578

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0772

Alfa AF: 0.0731 Hom.: 73

Bravo AF: 0.0629

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 05, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.6
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.048
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: rs74633160; hg19: chr9-114341240;