10-119423068-T-C

Variant names:

• chr10-119423068-T-C
• rs11198918
• NM_005308.3:c.340-98T>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.340-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 773,052 control chromosomes in the GnomAD database, including 2,899 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 0.055 (405 hom., cov: 33)
  • Exomes 𝑓: 0.075 (2494 hom.)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005308.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	NM_005308.3	MANE Select	c.340-98T>C		intron	N/A	NP_005299.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	ENST00000392870.3	TSL:1 MANE Select	c.340-98T>C		intron	N/A	ENSP00000376609.2

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8321 AN: 152178 Hom.: 406 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.0748 AC: 46407 AN: 620756 Hom.: 2494 AF XY: 0.0784 AC XY: 26064 AN XY: 332262

African (AFR) AF: 0.0127 AC: 223 AN: 17510

American (AMR) AF: 0.0425 AC: 1728 AN: 40628

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 690 AN: 18468

East Asian (EAS) AF: 0.209 AC: 7407 AN: 35500

South Asian (SAS) AF: 0.145 AC: 9192 AN: 63356

European-Finnish (FIN) AF: 0.0474 AC: 2078 AN: 43820

Middle Eastern (MID) AF: 0.0339 AC: 110 AN: 3244

European-Non Finnish (NFE) AF: 0.0623 AC: 22801 AN: 365940

Other (OTH) AF: 0.0675 AC: 2178 AN: 32290

GnomAD4 genome AF: 0.0546 AC: 8320 AN: 152296 Hom.: 405 Cov.: 33 AF XY: 0.0563 AC XY: 4195 AN XY: 74478

African (AFR) AF: 0.0126 AC: 525 AN: 41572

American (AMR) AF: 0.0426 AC: 652 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1198 AN: 5164

South Asian (SAS) AF: 0.155 AC: 748 AN: 4830

European-Finnish (FIN) AF: 0.0477 AC: 507 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0650 AC: 4420 AN: 68020

Other (OTH) AF: 0.0468 AC: 99 AN: 2116

Alfa AF: 0.0586 Hom.: 55

Bravo AF: 0.0501

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.56
PhyloP100		-2.2
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: rs11198918; hg19: chr10-121182580; COSMIC: COSV64868251;