rs1481280

Variant names:

• chr18-21075490-C-A
• rs1481280
• NM_005406.3:c.94-4877G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 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.94-4877G>T		intron	N/A	NP_005397.1	Q13464

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	ENST00000399799.3	TSL:1 MANE Select	c.94-4877G>T		intron	N/A	ENSP00000382697.1	Q13464
	ROCK1	ENST00000635540.2	TSL:5	n.94-4877G>T		intron	N/A	ENSP00000489185.1	A0A0U1RQV4

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

African (AFR) AF: 0.130 AC: 5379 AN: 41504

American (AMR) AF: 0.370 AC: 5655 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1132 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1894 AN: 5172

South Asian (SAS) AF: 0.465 AC: 2241 AN: 4816

European-Finnish (FIN) AF: 0.448 AC: 4721 AN: 10532

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26534 AN: 67956

Other (OTH) AF: 0.339 AC: 715 AN: 2110

Alfa AF: 0.368 Hom.: 18874

Bravo AF: 0.304

Asia WGS AF: 0.462 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		-1.2
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: rs1481280; hg19: chr18-18655451;