rs1481280

Positions:

• chr18-21075490-C-A

Variant summary

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

The NM_005406.3(ROCK1):​c.94-4877G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,040 control chromosomes in the GnomAD database, including 8,923 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 0.32 (8923 hom., cov: 32)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROCK1	NM_005406.3	c.94-4877G>T		intron_variant		ENST00000399799.3	NP_005397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROCK1	ENST00000399799.3	c.94-4877G>T		intron_variant		1	NM_005406.3	ENSP00000382697	P1
ROCK1	ENST00000635540.2	c.94-4877G>T		intron_variant, NMD_transcript_variant		5		ENSP00000489185

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48640 AN: 151922 Hom.: 8923 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.320 AC: 48645 AN: 152040 Hom.: 8923 Cov.: 32 AF XY: 0.327 AC XY: 24273 AN XY: 74304

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.339

Alfa AF: 0.376 Hom.: 15487

Bravo AF: 0.304

Asia WGS AF: 0.462 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.33

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: rs1481280; hg19: chr18-18655451;