10-119423276-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005308.3(GRK5):c.440+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,591,576 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.136

Genes affected

GRK5 (HGNC:4544): (G protein-coupled receptor kinase 5) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-119423276-G-A is Benign according to our data. Variant chr10-119423276-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 730648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3	c.440+10G>A		intron_variant		ENST00000392870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3	c.440+10G>A		intron_variant		1	NM_005308.3	P1

Frequencies

GnomAD3 genomes AF: 0.000848 AC: 129 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000800 AC: 201 AN: 251266 Hom.: 0 AF XY: 0.000825 AC XY: 112 AN XY: 135796

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.000926

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00105 AC: 1511 AN: 1439262 Hom.: 1 Cov.: 26 AF XY: 0.00111 AC XY: 798 AN XY: 717550

Gnomad4 AFR exome AF: 0.0000606

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00204

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00127

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.000847 AC: 129 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.000792 AC XY: 59 AN XY: 74468

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.000793

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.2
Dann	Benign	0.69

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: rs200231122; hg19: chr10-121182788;