Variant 1-110454050-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032414.3(PROK1):c.162G>T(p.Gly54Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,614,008 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 84 hom. )

Consequence

PROK1
NM_032414.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.27

Variant links:

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]

PROK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-110454050-G-T is Benign according to our data. Variant chr1-110454050-G-T is described in ClinVar as [Benign]. Clinvar id is 717610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.27 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00365 (556/152358) while in subpopulation SAS AF= 0.0244 (118/4832). AF 95% confidence interval is 0.0208. There are 1 homozygotes in gnomad4. There are 296 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 84 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROK1	NM_032414.3 linkuse as main transcript	c.162G>T	p.Gly54Gly	synonymous_variant	2/3	ENST00000271331.4	NP_115790.1	P58294A0A024R0B1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROK1	ENST00000271331.4 linkuse as main transcript	c.162G>T	p.Gly54Gly	synonymous_variant	2/3	1	NM_032414.3	ENSP00000271331.3		P58294

Frequencies

GnomAD3 genomes

AF:

0.00366

AC:

557

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000916

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0246

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00465

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00609

AC:

1528

AN:

250762

Hom.:

AF XY:

0.00710

AC XY:

964

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.000929

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.00567

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00457

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00612

AC:

8939

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

4860

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00524

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0258

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.00524

Gnomad4 OTH exome

AF:

0.00740

GnomAD4 genome

AF:

0.00365

AC:

556

AN:

152358

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

296

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0244

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00465

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00445

Hom.:

Bravo

AF:

0.00319

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.74

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over