9-5410723-C-T

Variant names:

• chr9-5410723-C-T
• rs1535454
• NM_018465.4:c.81+21174G>A

Variant summary

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

The NM_018465.4(PLGRKT):​c.81+21174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 152,114 control chromosomes in the GnomAD database, including 445 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 0.067 (445 hom., cov: 32)
• Consequence: PLGRKT NM_018465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 4 publications found

Genes affected

PLGRKT (HGNC:23633): (plasminogen receptor with a C-terminal lysine) Predicted to be involved in positive regulation of plasminogen activation. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLGRKT	NM_018465.4	c.81+21174G>A		intron_variant	Intron 3 of 5	ENST00000223864.7	NP_060935.2
PLGRKT	XM_005251510.6	c.81+21174G>A		intron_variant	Intron 3 of 5		XP_005251567.1
PLGRKT	XM_011517960.3	c.81+21174G>A		intron_variant	Intron 3 of 5		XP_011516262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLGRKT	ENST00000223864.7	c.81+21174G>A		intron_variant	Intron 3 of 5	1	NM_018465.4	ENSP00000223864.2
PLGRKT	ENST00000472145.5	n.288+21174G>A		intron_variant	Intron 3 of 3	2
PLGRKT	ENST00000473877.1	n.214-18074G>A		intron_variant	Intron 2 of 2	3
PLGRKT	ENST00000482696.5	n.292+21174G>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10224 AN: 151996 Hom.: 444 Cov.: 32

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0789

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0673 AC: 10232 AN: 152114 Hom.: 445 Cov.: 32 AF XY: 0.0686 AC XY: 5100 AN XY: 74376

African (AFR) AF: 0.0880 AC: 3651 AN: 41488

American (AMR) AF: 0.0621 AC: 949 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3468

East Asian (EAS) AF: 0.148 AC: 765 AN: 5170

South Asian (SAS) AF: 0.161 AC: 775 AN: 4808

European-Finnish (FIN) AF: 0.0345 AC: 365 AN: 10574

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0454 AC: 3088 AN: 67996

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0596 Hom.: 475

Bravo AF: 0.0702

Asia WGS AF: 0.176 AC: 612 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.76
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs1535454; hg19: chr9-5410723; COSMIC: COSV56352205;