chr18-21073649-C-T

Variant names:

• chr18-21073649-C-T
• rs2127958
• NM_005406.3:c.94-3036G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005406.3(ROCK1):​c.94-3036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,864 control chromosomes in the GnomAD database, including 17,159 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 0.45 (17159 hom., cov: 31)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	NM_005406.3	MANE Select	c.94-3036G>A		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.94-3036G>A		intron	N/A	ENSP00000382697.1
	ROCK1	ENST00000635540.2	TSL:5	n.94-3036G>A		intron	N/A	ENSP00000489185.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68885 AN: 151746 Hom.: 17165 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.454 AC: 68881 AN: 151864 Hom.: 17159 Cov.: 31 AF XY: 0.450 AC XY: 33395 AN XY: 74198

African (AFR) AF: 0.236 AC: 9784 AN: 41428

American (AMR) AF: 0.421 AC: 6418 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2798 AN: 5168

South Asian (SAS) AF: 0.472 AC: 2269 AN: 4810

European-Finnish (FIN) AF: 0.519 AC: 5455 AN: 10516

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38457 AN: 67902

Other (OTH) AF: 0.470 AC: 989 AN: 2104

Alfa AF: 0.533 Hom.: 19273

Bravo AF: 0.438

Asia WGS AF: 0.419 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		-0.15
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: rs2127958; hg19: chr18-18653610;