rs288979

chr18-21031282-A-G

Variant summary

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

The NM_005406.3(ROCK1):c.1052-2347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,104 control chromosomes in the GnomAD database, including 7,206 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 0.21 (7206 hom., cov: 31)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

ROCK1 (HGNC:10251): (Rho associated coiled-coil containing protein kinase 1) This gene encodes a protein serine/threonine kinase that is activated when bound to the GTP-bound form of Rho. The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor. This protein, a downstream effector of Rho, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. A pseudogene, related to this gene, is also located on chromosome 18. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK1	NM_005406.3	c.1052-2347T>C		intron_variant		ENST00000399799.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK1	ENST00000399799.3	c.1052-2347T>C		intron_variant		1	NM_005406.3	P1
ROCK1	ENST00000635540.2	c.1052-2347T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31156 AN: 151986 Hom.: 7169 Cov.: 31

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.0872

Gnomad SAS AF: 0.0497

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.206 AC: 31259 AN: 152104 Hom.: 7206 Cov.: 31 AF XY: 0.202 AC XY: 15028 AN XY: 74412

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.0985

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.0501

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.176

Alfa AF: 0.119 Hom.: 953

Bravo AF: 0.236

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.61
Dann	Benign	0.58

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: rs288979; hg19: chr18-18611243;