rs2488815

Variant names:

• chr4-2986909-C-A
• rs2488815
• NM_182982.3:c.149-1818C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-2986909-C-A
• chr4-2986909-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182982.3(GRK4):​c.149-1818C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRK4 NM_182982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 13 publications found

Genes affected

GRK4 (HGNC:4543): (G protein-coupled receptor kinase 4) 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 its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK4	NM_182982.3	c.149-1818C>A		intron_variant	Intron 2 of 15	ENST00000398052.9	NP_892027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK4	ENST00000398052.9	c.149-1818C>A		intron_variant	Intron 2 of 15	1	NM_182982.3	ENSP00000381129.4
GRK4	ENST00000345167.10	c.53-1818C>A		intron_variant	Intron 1 of 14	1		ENSP00000264764.8
GRK4	ENST00000504933.1	c.149-1818C>A		intron_variant	Intron 2 of 14	1		ENSP00000427445.1
GRK4	ENST00000398051.8	c.53-1818C>A		intron_variant	Intron 1 of 13	1		ENSP00000381128.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 148970 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 83878

African (AFR) AF: 0.00 AC: 0 AN: 3920

American (AMR) AF: 0.00 AC: 0 AN: 6520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3684

East Asian (EAS) AF: 0.00 AC: 0 AN: 6240

South Asian (SAS) AF: 0.00 AC: 0 AN: 31412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1998

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 81230

Other (OTH) AF: 0.00 AC: 0 AN: 7028

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 6754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.16
PhyloP100		-1.3

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: rs2488815; hg19: chr4-2988636;