rs7513898

chr1-110456043-G-Achr1-110456043-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032414.3(PROK1):c.199-189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,058 control chromosomes in the GnomAD database, including 19,299 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 0.49 (19299 hom., cov: 32)
• Consequence: PROK1 NM_032414.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

Genes affected

PROK1 (HGNC:18454): (prokineticin 1) The protein encoded by this gene induces proliferation, migration, and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. It has little or no effect on a variety of other endothelial and non-endothelial cell types. Its expression is restricted to the steroidogenic glands (ovary, testis, adrenal, and placenta), is induced by hypoxia, and often complementary to the expression of vascular endothelial growth factor (VEGF), suggesting that these molecules function in a coordinated manner. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROK1	NM_032414.3	c.199-189G>A		intron_variant		ENST00000271331.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROK1	ENST00000271331.4	c.199-189G>A		intron_variant		1	NM_032414.3	P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74986 AN: 151940 Hom.: 19280 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.494 AC: 75065 AN: 152058 Hom.: 19299 Cov.: 32 AF XY: 0.493 AC XY: 36625 AN XY: 74304

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.479

Alfa AF: 0.457 Hom.: 2218

Bravo AF: 0.515

Asia WGS AF: 0.464 AC: 1616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.18
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs7513898; hg19: chr1-110998665;