11-67271141-T-C

Variant names:

• chr11-67271141-T-C
• rs1894111
• NM_001619.5:c.113+4329T>C

Variant summary

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

The NM_001619.5(GRK2):​c.113+4329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 152,426 control chromosomes in the GnomAD database, including 69,425 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 0.95 (69338 hom., cov: 31)
  • Exomes 𝑓: 0.98 (87 hom.)
• Consequence: GRK2 NM_001619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK2	NM_001619.5	c.113+4329T>C		intron_variant	Intron 1 of 20	ENST00000308595.10	NP_001610.2
GRK2	XM_011544773.2	c.23+3293T>C		intron_variant	Intron 1 of 20		XP_011543075.1
GRK2	XR_007062455.1	n.340+4329T>C		intron_variant	Intron 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK2	ENST00000308595.10	c.113+4329T>C		intron_variant	Intron 1 of 20	1	NM_001619.5	ENSP00000312262.5
GRK2	ENST00000526285.1	c.113+4329T>C		intron_variant	Intron 1 of 13	5		ENSP00000434126.1
GRK2	ENST00000530291.5	n.71+133T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.953 AC: 145031 AN: 152126 Hom.: 69306 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.962

GnomAD4 exome AF: 0.978 AC: 178 AN: 182 Hom.: 87 AF XY: 0.991 AC XY: 107 AN XY: 108

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 0.962

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.967

GnomAD4 genome AF: 0.953 AC: 145115 AN: 152244 Hom.: 69338 Cov.: 31 AF XY: 0.952 AC XY: 70847 AN XY: 74436

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.989

Gnomad4 OTH AF: 0.961

Alfa AF: 0.967 Hom.: 17036

Bravo AF: 0.949

Asia WGS AF: 0.909 AC: 3163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.021
DANN	Benign	0.85

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: rs1894111; hg19: chr11-67038612;