9-122371212-TTCCTGC-T

Variant names:

• chr9-122371212-TTCCTGC-T
• rs534752292
• NM_000962.4:c.44_49delTGCTCC

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_000962.4(PTGS1):​c.44_49delTGCTCC​(p.Leu15_Leu16del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,608,470 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (38 hom.)
• Consequence: PTGS1 NM_000962.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.31
• Publications: 4 publications found

Genes affected

PTGS1 (HGNC:9604): (prostaglandin-endoperoxide synthase 1) This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]

PTGS1 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 12

  Inheritance: AR, AD, SD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000962.4
• BP6: Variant 9-122371212-TTCCTGC-T is Benign according to our data. Variant chr9-122371212-TTCCTGC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 710745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000962.4. 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
	PTGS1	NM_000962.4	MANE Select	c.44_49delTGCTCC	p.Leu15_Leu16del	disruptive_inframe_deletion	Exon 2 of 11	NP_000953.2
	PTGS1	NM_080591.3		c.44_49delTGCTCC	p.Leu15_Leu16del	disruptive_inframe_deletion	Exon 2 of 11	NP_542158.1	P23219-2
	PTGS1	NM_001271164.2		c.44_49delTGCTCC	p.Leu15_Leu16del	disruptive_inframe_deletion	Exon 2 of 10	NP_001258093.1	A0A087X296

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.44_49delTGCTCC	p.Leu15_Leu16del	disruptive_inframe_deletion	Exon 2 of 11	ENSP00000354612.2	P23219-1
	PTGS1	ENST00000223423.8	TSL:1	c.44_49delTGCTCC	p.Leu15_Leu16del	disruptive_inframe_deletion	Exon 2 of 11	ENSP00000223423.4	P23219-2
	PTGS1	ENST00000863393.1		c.44_49delTGCTCC	p.Leu15_Leu16del	disruptive_inframe_deletion	Exon 2 of 12	ENSP00000533452.1

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 594 AN: 152208 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00405 AC: 1000 AN: 246998 AF XY: 0.00409

Gnomad AFR exome AF: 0.000804

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00407

Gnomad NFE exome AF: 0.00632

Gnomad OTH exome AF: 0.00574

GnomAD4 exome AF: 0.00619 AC: 9015 AN: 1456146 Hom.: 38 AF XY: 0.00612 AC XY: 4438 AN XY: 724644

African (AFR) AF: 0.000627 AC: 21 AN: 33472

American (AMR) AF: 0.00284 AC: 127 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00509 AC: 133 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.00110 AC: 95 AN: 86254

European-Finnish (FIN) AF: 0.00451 AC: 216 AN: 47920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00723 AC: 8043 AN: 1111842

Other (OTH) AF: 0.00626 AC: 378 AN: 60352

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152324 Hom.: 4 Cov.: 33 AF XY: 0.00373 AC XY: 278 AN XY: 74488

African (AFR) AF: 0.000938 AC: 39 AN: 41584

American (AMR) AF: 0.00281 AC: 43 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00666 AC: 453 AN: 68006

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00544 Hom.: 1

Bravo AF: 0.00385

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely 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
PhyloP100		3.3
Mutation Taster		=195/5	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs534752292; hg19: chr9-125133491; COSMIC: COSV56291679; COSMIC: COSV56291679;