rs1467200

Positions:

• chr3-141784322-A-G

Variant summary

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

The NM_139209.3(GRK7):​c.1050+3511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,090 control chromosomes in the GnomAD database, including 11,926 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 0.32 (11926 hom., cov: 32)
• Consequence: GRK7 NM_139209.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

Genes affected

GRK7 (HGNC:17031): (G protein-coupled receptor kinase 7) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. It is specifically expressed in the retina and the encoded protein has been shown to phosphorylate cone opsins and initiate their deactivation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK7	NM_139209.3	c.1050+3511A>G		intron_variant		ENST00000682958.1	NP_631948.1
GRK7	XM_047447449.1	c.1050+3511A>G		intron_variant			XP_047303405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK7	ENST00000682958.1	c.1050+3511A>G		intron_variant			NM_139209.3	ENSP00000508022	P1
GRK7	ENST00000264952.2	c.1050+3511A>G		intron_variant		1		ENSP00000264952	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48977 AN: 151972 Hom.: 11882 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.323 AC: 49065 AN: 152090 Hom.: 11926 Cov.: 32 AF XY: 0.314 AC XY: 23361 AN XY: 74372

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.281

Alfa AF: 0.273 Hom.: 1093

Bravo AF: 0.344

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.44

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: rs1467200; hg19: chr3-141503164; COSMIC: COSV53825566;