9-122371212-TTCCTGC-T

Position:

• chr9-122371212-TTCCTGC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000962.4(PTGS1):​c.44_49del​(p.Leu15_Leu16del) variant causes a 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 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.31

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• 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 id is 710745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.44_49del	p.Leu15_Leu16del	inframe_deletion	2/11	ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.44_49del	p.Leu15_Leu16del	inframe_deletion	2/11	1	NM_000962.4	P1

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

GnomAD3 exomes AF: 0.00405 AC: 1000 AN: 246998 Hom.: 5 AF XY: 0.00409 AC XY: 547 AN XY: 133866

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 SAS exome AF: 0.000947

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

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.00509

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.00451

Gnomad4 NFE exome AF: 0.00723

Gnomad4 OTH exome AF: 0.00626

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

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00544 Hom.: 1

Bravo AF: 0.00385

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs534752292; hg19: chr9-125133491;