rs6085086

Positions:

• chr20-5312480-G-A
• chr20-5312480-G-C

Variant summary

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

The NM_144773.4(PROKR2):​c.458+1432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,110 control chromosomes in the GnomAD database, including 7,385 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 0.31 (7385 hom., cov: 33)
• Consequence: PROKR2 NM_144773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

Genes affected

PROKR2 (HGNC:15836): (prokineticin receptor 2) Prokineticins are secreted proteins that can promote angiogenesis and induce strong gastrointestinal smooth muscle contraction. The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor for prokineticins. The encoded protein is similar in sequence to GPR73, another G protein-coupled receptor for prokineticins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROKR2	NM_144773.4	c.458+1432C>T		intron_variant		ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2	c.458+1432C>T		intron_variant			XP_016883135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROKR2	ENST00000678254.1	c.458+1432C>T		intron_variant			NM_144773.4	ENSP00000504128	P1
PROKR2	ENST00000217270.4	c.458+1432C>T		intron_variant		1		ENSP00000217270	P1
PROKR2	ENST00000678059.1	c.350+1432C>T		intron_variant				ENSP00000503366

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46631 AN: 151992 Hom.: 7376 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.307 AC: 46659 AN: 152110 Hom.: 7385 Cov.: 33 AF XY: 0.305 AC XY: 22646 AN XY: 74350

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.308

Alfa AF: 0.230 Hom.: 660

Bravo AF: 0.298

Asia WGS AF: 0.298 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.75

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: rs6085086; hg19: chr20-5293126;