rs11198893

Variant names:

• chr10-119348388-G-A
• rs11198893
• NM_005308.3:c.148+21777G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-119348388-G-A
• chr10-119348388-G-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.148+21777G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,156 control chromosomes in the GnomAD database, including 536 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 0.068 (536 hom., cov: 33)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK5	NM_005308.3	c.148+21777G>A		intron_variant	Intron 2 of 15	ENST00000392870.3	NP_005299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3	c.148+21777G>A		intron_variant	Intron 2 of 15	1	NM_005308.3	ENSP00000376609.2

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10322 AN: 152038 Hom.: 535 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0678 AC: 10322 AN: 152156 Hom.: 536 Cov.: 33 AF XY: 0.0705 AC XY: 5241 AN XY: 74390

African (AFR) AF: 0.0148 AC: 612 AN: 41464

American (AMR) AF: 0.0413 AC: 632 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 123 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1191 AN: 5158

South Asian (SAS) AF: 0.133 AC: 639 AN: 4818

European-Finnish (FIN) AF: 0.0907 AC: 962 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0885 AC: 6018 AN: 68018

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0754 Hom.: 854

Bravo AF: 0.0615

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.76
PhyloP100		0.52
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: rs11198893; hg19: chr10-121107900;