rs288979

Variant names:

• chr18-21031282-A-G
• rs288979
• NM_005406.3:c.1052-2347T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005406.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	NM_005406.3	MANE Select	c.1052-2347T>C		intron	N/A	NP_005397.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	ENST00000399799.3	TSL:1 MANE Select	c.1052-2347T>C		intron	N/A	ENSP00000382697.1
	ROCK1	ENST00000635540.2	TSL:5	n.1052-2347T>C		intron	N/A	ENSP00000489185.1

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

African (AFR) AF: 0.568 AC: 23548 AN: 41424

American (AMR) AF: 0.201 AC: 3072 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0985 AC: 342 AN: 3472

East Asian (EAS) AF: 0.0880 AC: 455 AN: 5170

South Asian (SAS) AF: 0.0501 AC: 242 AN: 4826

European-Finnish (FIN) AF: 0.0331 AC: 352 AN: 10622

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.0413 AC: 2805 AN: 67996

Other (OTH) AF: 0.176 AC: 372 AN: 2114

Alfa AF: 0.127 Hom.: 1075

Bravo AF: 0.236

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.58
PhyloP100		-1.4
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: rs288979; hg19: chr18-18611243;