rs4648291

Variant names:

• chr1-186674071-TTATAA-T
• rs4648291
• ENST00000490885.6:n.2507_2511delTTATA

Your query was ambiguous. Multiple possible variants found:

• chr1-186674071-TTATAA-T
• chr1-186674071-TTATAA-TTATAATATAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000490885.6(PTGS2):​n.2507_2511delTTATA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 171,644 control chromosomes in the GnomAD database, including 3,165 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (3109 hom., cov: 31)
  • Exomes 𝑓: 0.019 (56 hom.)
• Consequence: PTGS2 ENST00000490885.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 3 publications found

Genes affected

PTGS2 (HGNC:9605): (prostaglandin-endoperoxide synthase 2) Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490885.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.*277_*281delTTATA		3_prime_UTR	Exon 10 of 10	NP_000954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000490885.6	TSL:1	n.2507_2511delTTATA		non_coding_transcript_exon	Exon 9 of 9
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.*277_*281delTTATA		3_prime_UTR	Exon 10 of 10	ENSP00000356438.5
	PTGS2	ENST00000681605.1		n.*1764_*1768delTTATA		non_coding_transcript_exon	Exon 10 of 10	ENSP00000504900.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17211 AN: 151872 Hom.: 3088 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0843

GnomAD4 exome AF: 0.0187 AC: 368 AN: 19654 Hom.: 56 AF XY: 0.0158 AC XY: 170 AN XY: 10738

African (AFR) AF: 0.402 AC: 258 AN: 642

American (AMR) AF: 0.0297 AC: 22 AN: 740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 778

East Asian (EAS) AF: 0.000650 AC: 1 AN: 1538

South Asian (SAS) AF: 0.0490 AC: 10 AN: 204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1004

Middle Eastern (MID) AF: 0.0119 AC: 1 AN: 84

European-Non Finnish (NFE) AF: 0.00157 AC: 21 AN: 13410

Other (OTH) AF: 0.0439 AC: 55 AN: 1254

GnomAD4 genome AF: 0.114 AC: 17271 AN: 151990 Hom.: 3109 Cov.: 31 AF XY: 0.110 AC XY: 8151 AN XY: 74360

African (AFR) AF: 0.390 AC: 16112 AN: 41280

American (AMR) AF: 0.0430 AC: 657 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 68008

Other (OTH) AF: 0.0834 AC: 176 AN: 2110

Alfa AF: 0.0938 Hom.: 256

Bravo AF: 0.130

Asia WGS AF: 0.0430 AC: 150 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4648291; hg19: chr1-186643203;