rs2731672

Positions:

• chr5-177415473-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502598.5(GRK6):​c.-45+11947T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,124 control chromosomes in the GnomAD database, including 34,232 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 0.66 (34232 hom., cov: 32)
• Consequence: GRK6 ENST00000502598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296

Genes affected

GRK6 (HGNC:4545): (G protein-coupled receptor kinase 6) 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. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.177415473T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK6	ENST00000506296.5	c.-45+10916T>C		intron_variant		5		ENSP00000421055.1
GRK6	ENST00000502598.5	c.-45+11947T>C		intron_variant		4		ENSP00000422873.1
F12	ENST00000696200.1	n.78+1033A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99916 AN: 152006 Hom.: 34222 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.657 AC: 99964 AN: 152124 Hom.: 34232 Cov.: 32 AF XY: 0.652 AC XY: 48482 AN XY: 74368

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.691

Alfa AF: 0.730 Hom.: 87396

Bravo AF: 0.649

Asia WGS AF: 0.395 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2731672; hg19: chr5-176842474;