rs7128315

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001619.5(GRK2):​c.114-3545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0864 in 152,188 control chromosomes in the GnomAD database, including 1,927 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 0.086 ( 1927 hom., cov: 32)

Consequence

GRK2
NM_001619.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190
Variant links:
Genes affected
GRK2 (HGNC:289): (G protein-coupled receptor kinase 2) This gene encodes a member of the G protein-coupled receptor kinase family of proteins. The encoded protein phosphorylates the beta-adrenergic receptor as well as a wide range of other substrates including non-GPCR cell surface receptors, and cytoskeletal, mitochondrial, and transcription factor proteins. Data from rodent models supports a role for this gene in embryonic development, heart function and metabolism. Elevated expression of this gene has been observed in human patients with heart failure and Alzheimer's disease. [provided by RefSeq, Sep 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GRK2NM_001619.5 linkuse as main transcriptc.114-3545G>A intron_variant ENST00000308595.10 NP_001610.2
GRK2XM_011544773.2 linkuse as main transcriptc.24-3545G>A intron_variant XP_011543075.1
GRK2XR_007062455.1 linkuse as main transcriptn.341-3545G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GRK2ENST00000308595.10 linkuse as main transcriptc.114-3545G>A intron_variant 1 NM_001619.5 ENSP00000312262 P1
GRK2ENST00000526285.1 linkuse as main transcriptc.114-3545G>A intron_variant 5 ENSP00000434126
GRK2ENST00000530291.5 linkuse as main transcriptn.71+2719G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0864
AC:
13134
AN:
152070
Hom.:
1925
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.300
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0339
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00104
Gnomad OTH
AF:
0.0580
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0864
AC:
13154
AN:
152188
Hom.:
1927
Cov.:
32
AF XY:
0.0825
AC XY:
6142
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.300
Gnomad4 AMR
AF:
0.0337
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00104
Gnomad4 OTH
AF:
0.0574
Alfa
AF:
0.0686
Hom.:
180
Bravo
AF:
0.0966
Asia WGS
AF:
0.0120
AC:
43
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
6.4
DANN
Benign
0.57
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7128315; hg19: chr11-67041198; API