chr5-177429924-T-G

Variant names:

• chr5-177429924-T-G
• rs13177732
• NM_001004106.3:c.53-948T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004106.3. 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
	GRK6	NM_001004106.3	MANE Select	c.53-948T>G		intron	N/A	NP_001004106.1
	GRK6	NM_002082.4		c.53-948T>G		intron	N/A	NP_002073.2
	GRK6	NM_001004105.3		c.53-948T>G		intron	N/A	NP_001004105.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK6	ENST00000355472.10	TSL:1 MANE Select	c.53-948T>G		intron	N/A	ENSP00000347655.5
	GRK6	ENST00000528793.5	TSL:1	c.53-948T>G		intron	N/A	ENSP00000433511.1
	GRK6	ENST00000355958.9	TSL:1	c.53-948T>G		intron	N/A	ENSP00000348230.5

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

African (AFR) AF: 0.0454 AC: 1884 AN: 41524

American (AMR) AF: 0.146 AC: 2235 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.103 AC: 499 AN: 4828

European-Finnish (FIN) AF: 0.155 AC: 1638 AN: 10584

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.240 AC: 16303 AN: 67980

Other (OTH) AF: 0.183 AC: 386 AN: 2108

Alfa AF: 0.202 Hom.: 2381

Bravo AF: 0.156

Asia WGS AF: 0.0490 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.79
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: rs13177732; hg19: chr5-176856925;