chr5-177429924-T-G

Position:

• chr5-177429924-T-G

Variant summary

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

The NM_001004106.3(GRK6):​c.53-948T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,160 control chromosomes in the GnomAD database, including 2,521 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 0.16 (2521 hom., cov: 32)
• Consequence: GRK6 NM_001004106.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK6	NM_001004106.3	c.53-948T>G		intron_variant		ENST00000355472.10	NP_001004106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK6	ENST00000355472.10	c.53-948T>G		intron_variant		1	NM_001004106.3	ENSP00000347655	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24110 AN: 152054 Hom.: 2523 Cov.: 32

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.158 AC: 24101 AN: 152160 Hom.: 2521 Cov.: 32 AF XY: 0.152 AC XY: 11301 AN XY: 74384

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.183

Alfa AF: 0.213 Hom.: 1658

Bravo AF: 0.156

Asia WGS AF: 0.0490 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.79

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: rs13177732; hg19: chr5-176856925;