18-21090766-G-A

Variant names:

• chr18-21090766-G-A
• rs1552110
• NM_005406.3:c.93+20052C>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.93+20052C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,086 control chromosomes in the GnomAD database, including 52,214 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 0.80 (52214 hom., cov: 32)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.953 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	NM_005406.3	MANE Select	c.93+20052C>T		intron	N/A	NP_005397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	ENST00000399799.3	TSL:1 MANE Select	c.93+20052C>T		intron	N/A	ENSP00000382697.1
	ROCK1	ENST00000635540.2	TSL:5	n.93+20052C>T		intron	N/A	ENSP00000489185.1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121270 AN: 151968 Hom.: 52220 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.798 AC: 121294 AN: 152086 Hom.: 52214 Cov.: 32 AF XY: 0.801 AC XY: 59567 AN XY: 74370

African (AFR) AF: 0.442 AC: 18308 AN: 41402

American (AMR) AF: 0.800 AC: 12235 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3130 AN: 3472

East Asian (EAS) AF: 0.912 AC: 4714 AN: 5170

South Asian (SAS) AF: 0.950 AC: 4585 AN: 4826

European-Finnish (FIN) AF: 0.967 AC: 10252 AN: 10604

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.959 AC: 65202 AN: 68010

Other (OTH) AF: 0.823 AC: 1735 AN: 2108

Alfa AF: 0.808 Hom.: 11348

Bravo AF: 0.767

Asia WGS AF: 0.890 AC: 3092 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.45
DANN	Benign	0.43
PhyloP100		-0.48
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: rs1552110; hg19: chr18-18670727;