NM_000962.4:c.95-2483A>T

Variant names:

• chr9-122375416-A-T
• rs10306135
• NM_000962.4:c.95-2483A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000962.4(PTGS1):​c.95-2483A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 985,268 control chromosomes in the GnomAD database, including 9,412 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1644 hom., cov: 32)
  • Exomes 𝑓: 0.14 (7768 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 21 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: SD, AD, AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

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.95-2483A>T		intron	N/A	NP_000953.2
	PTGS1	NM_001271165.2		c.-262A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001258094.1	P23219-4
	PTGS1	NM_001271165.2		c.-262A>T		5_prime_UTR	Exon 1 of 10	NP_001258094.1	P23219-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.95-2483A>T		intron	N/A	ENSP00000354612.2	P23219-1
	PTGS1	ENST00000223423.8	TSL:1	c.95-2483A>T		intron	N/A	ENSP00000223423.4	P23219-2
	PTGS1	ENST00000373698.7	TSL:2	c.-262A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000362802.5	P23219-4

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21490 AN: 152070 Hom.: 1645 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.136 AC: 113032 AN: 833080 Hom.: 7768 Cov.: 30 AF XY: 0.136 AC XY: 52334 AN XY: 384706

African (AFR) AF: 0.149 AC: 2359 AN: 15780

American (AMR) AF: 0.118 AC: 116 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 711 AN: 5152

East Asian (EAS) AF: 0.0121 AC: 44 AN: 3630

South Asian (SAS) AF: 0.177 AC: 2907 AN: 16460

European-Finnish (FIN) AF: 0.101 AC: 28 AN: 276

Middle Eastern (MID) AF: 0.113 AC: 183 AN: 1622

European-Non Finnish (NFE) AF: 0.135 AC: 103205 AN: 761886

Other (OTH) AF: 0.127 AC: 3479 AN: 27290

GnomAD4 genome AF: 0.141 AC: 21522 AN: 152188 Hom.: 1644 Cov.: 32 AF XY: 0.140 AC XY: 10409 AN XY: 74404

African (AFR) AF: 0.147 AC: 6106 AN: 41528

American (AMR) AF: 0.132 AC: 2015 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5162

South Asian (SAS) AF: 0.170 AC: 817 AN: 4820

European-Finnish (FIN) AF: 0.132 AC: 1398 AN: 10592

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10104 AN: 67992

Other (OTH) AF: 0.161 AC: 340 AN: 2112

Alfa AF: 0.162 Hom.: 257

Bravo AF: 0.137

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.83
PhyloP100		-0.17
PromoterAI		0.021	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs10306135; hg19: chr9-125137695;