chr10-119430601-T-C

Variant names:

• chr10-119430601-T-C
• rs915120
• NM_005308.3:c.597+163T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005308.3(GRK5):​c.597+163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,670 control chromosomes in the GnomAD database, including 17,077 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 0.47 (17077 hom., cov: 30)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK5	NM_005308.3	c.597+163T>C		intron_variant	Intron 7 of 15	ENST00000392870.3	NP_005299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3	c.597+163T>C		intron_variant	Intron 7 of 15	1	NM_005308.3	ENSP00000376609.2

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70684 AN: 151552 Hom.: 17053 Cov.: 30

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.467 AC: 70760 AN: 151670 Hom.: 17077 Cov.: 30 AF XY: 0.466 AC XY: 34560 AN XY: 74110

African (AFR) AF: 0.594 AC: 24587 AN: 41364

American (AMR) AF: 0.429 AC: 6537 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1527 AN: 3466

East Asian (EAS) AF: 0.551 AC: 2816 AN: 5110

South Asian (SAS) AF: 0.459 AC: 2207 AN: 4810

European-Finnish (FIN) AF: 0.376 AC: 3955 AN: 10522

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27671 AN: 67826

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.449 Hom.: 15335

Bravo AF: 0.475

Asia WGS AF: 0.534 AC: 1855 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.086
DANN	Benign	0.47
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs915120; hg19: chr10-121190113; COSMIC: COSV64865892;