10-119250744-A-G

Position:

• chr10-119250744-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005308.3(GRK5):​c.52+42775A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,244 control chromosomes in the GnomAD database, including 794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (794 hom., cov: 31)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.273

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-119250744-A-G is Benign according to our data. Variant chr10-119250744-A-G is described in ClinVar as [Benign]. Clinvar id is 1222037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK5	NM_005308.3	c.52+42775A>G		intron_variant		ENST00000392870.3	NP_005299.1
GRK5	XM_005269707.3	c.52+42775A>G		intron_variant			XP_005269764.1
GRK5	XM_005269708.2	c.52+42775A>G		intron_variant			XP_005269765.1
GRK5	XM_047425120.1	c.-264+42094A>G		intron_variant			XP_047281076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3	c.52+42775A>G		intron_variant		1	NM_005308.3	ENSP00000376609	P1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13304 AN: 152126 Hom.: 793 Cov.: 31

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0874 AC: 13300 AN: 152244 Hom.: 794 Cov.: 31 AF XY: 0.0841 AC XY: 6258 AN XY: 74426

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0484

Gnomad4 FIN AF: 0.0885

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.104

Alfa AF: 0.111 Hom.: 480

Bravo AF: 0.0850

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

This variant is associated with the following publications: (PMID: 32649856) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.64
DANN	Benign	0.67

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: rs10886430; hg19: chr10-121010256; COSMIC: COSV67313067;