NM_001146108.2:c.496-9T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146108.2(PTGR1):​c.496-9T>C variant causes a 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 intron
• Scores: Splicing: ADA: 0.0001471
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.46
• Publications: 1 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: Benign. The variant received -20 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 VariationId is 769755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

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>C		intron	N/A	NP_001139580.1	Q14914-1
	PTGR1	NM_012212.3		c.496-9T>C		intron	N/A	NP_036344.2	Q14914-1
	PTGR1	NM_001146109.2		c.496-9T>C		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>C		intron	N/A	ENSP00000385763.2	Q14914-1
	PTGR1	ENST00000309195.9	TSL:1	c.496-9T>C		intron	N/A	ENSP00000311572.5	Q14914-1
	PTGR1	ENST00000878676.1		c.496-9T>C		intron	N/A	ENSP00000548735.1

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

GnomAD2 exomes AF: 0.149 AC: 13974 AN: 93710 AF XY: 0.150

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.0900

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.141

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

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

African (AFR) AF: 0.0640 AC: 248 AN: 3872

American (AMR) AF: 0.349 AC: 2880 AN: 8256

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 786 AN: 3756

East Asian (EAS) AF: 0.409 AC: 5116 AN: 12522

South Asian (SAS) AF: 0.328 AC: 6748 AN: 20546

European-Finnish (FIN) AF: 0.263 AC: 3711 AN: 14100

Middle Eastern (MID) AF: 0.175 AC: 238 AN: 1358

European-Non Finnish (NFE) AF: 0.236 AC: 52574 AN: 222518

Other (OTH) AF: 0.265 AC: 3104 AN: 11732

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

African (AFR) AF: 0.0160 AC: 603 AN: 37650

American (AMR) AF: 0.116 AC: 1546 AN: 13350

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 173 AN: 3284

East Asian (EAS) AF: 0.211 AC: 1013 AN: 4794

South Asian (SAS) AF: 0.120 AC: 508 AN: 4248

European-Finnish (FIN) AF: 0.118 AC: 993 AN: 8400

Middle Eastern (MID) AF: 0.0629 AC: 18 AN: 286

European-Non Finnish (NFE) AF: 0.0710 AC: 4507 AN: 63456

Other (OTH) AF: 0.0772 AC: 144 AN: 1866

Alfa AF: 0.0731 Hom.: 73

Bravo AF: 0.0629

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.6
DANN	Benign	0.57
PhyloP100		1.5
Mutation Taster		=15/85	disease causing

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

Other links and lift over

dbSNP: rs74633160; hg19: chr9-114341240;