NM_139209.3:c.1050+3511A>G

Variant names:

• chr3-141784322-A-G
• rs1467200
• NM_139209.3:c.1050+3511A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000285558 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRK7	NM_139209.3	c.1050+3511A>G		intron_variant	Intron 4 of 5	ENST00000682958.1	NP_631948.1
GRK7	XM_047447449.1	c.1050+3511A>G		intron_variant	Intron 5 of 6		XP_047303405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK7	ENST00000682958.1	c.1050+3511A>G		intron_variant	Intron 4 of 5		NM_139209.3	ENSP00000508022.1
GRK7	ENST00000264952.2	c.1050+3511A>G		intron_variant	Intron 2 of 3	1		ENSP00000264952.2
ENSG00000285558	ENST00000648835.1	n.*391+3511A>G		intron_variant	Intron 2 of 2			ENSP00000498049.1

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

African (AFR) AF: 0.689 AC: 28541 AN: 41448

American (AMR) AF: 0.211 AC: 3232 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 685 AN: 3472

East Asian (EAS) AF: 0.104 AC: 539 AN: 5170

South Asian (SAS) AF: 0.190 AC: 915 AN: 4814

European-Finnish (FIN) AF: 0.124 AC: 1314 AN: 10602

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.191 AC: 12963 AN: 67990

Other (OTH) AF: 0.281 AC: 594 AN: 2112

Alfa AF: 0.267 Hom.: 2409

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
PhyloP100		-0.12
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: rs1467200; hg19: chr3-141503164; COSMIC: COSV53825566;