rs147964178

Variant names:

• chr9-136980066-C-T
• rs147964178
• NM_000954.6:c.448+4C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-136980066-C-T
• chr9-136980066-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000954.6(PTGDS):​c.448+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,610,182 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: PTGDS NM_000954.6 splice_region, intron
• Scores: Splicing: ADA: 0.0004218
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.958
• Publications: 0 publications found

Genes affected

PTGDS (HGNC:9592): (prostaglandin D2 synthase) The protein encoded by this gene is a glutathione-independent prostaglandin D synthase that catalyzes the conversion of prostaglandin H2 (PGH2) to postaglandin D2 (PGD2). PGD2 functions as a neuromodulator as well as a trophic factor in the central nervous system. PGD2 is also involved in smooth muscle contraction/relaxation and is a potent inhibitor of platelet aggregation. This gene is preferentially expressed in brain. Studies with transgenic mice overexpressing this gene suggest that this gene may be also involved in the regulation of non-rapid eye movement sleep. [provided by RefSeq, Jul 2008]

ENSG00000284341 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-136980066-C-T is Benign according to our data. Variant chr9-136980066-C-T is described in ClinVar as Benign. ClinVar VariationId is 785302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000954.6. 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
	PTGDS	NM_000954.6	MANE Select	c.448+4C>T		splice_region intron	N/A	NP_000945.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGDS	ENST00000371625.8	TSL:1 MANE Select	c.448+4C>T		splice_region intron	N/A	ENSP00000360687.3	P41222
	ENSG00000284341	ENST00000471521.5	TSL:5	n.448+4C>T		splice_region intron	N/A	ENSP00000435033.1
	PTGDS	ENST00000851752.1		c.1177+4C>T		splice_region intron	N/A	ENSP00000521811.1

Frequencies

GnomAD3 genomes AF: 0.00316 AC: 480 AN: 152114 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000784 AC: 194 AN: 247460 AF XY: 0.000568

Gnomad AFR exome AF: 0.0107

Gnomad AMR exome AF: 0.000379

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000627

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000281 AC: 409 AN: 1457950 Hom.: 2 Cov.: 31 AF XY: 0.000226 AC XY: 164 AN XY: 725258

African (AFR) AF: 0.0101 AC: 337 AN: 33414

American (AMR) AF: 0.000516 AC: 23 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.0000385 AC: 2 AN: 51926

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5744

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110346

Other (OTH) AF: 0.000547 AC: 33 AN: 60276

GnomAD4 genome AF: 0.00316 AC: 481 AN: 152232 Hom.: 3 Cov.: 33 AF XY: 0.00305 AC XY: 227 AN XY: 74432

African (AFR) AF: 0.0112 AC: 465 AN: 41540

American (AMR) AF: 0.000523 AC: 8 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67978

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000580 Hom.: 0

Bravo AF: 0.00324

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.91
PhyloP100		-0.96
PromoterAI		-0.10	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00042
dbscSNV1_RF	Benign	0.056
SpliceAI score (max)		0.060		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: rs147964178; hg19: chr9-139874518;