18-20980393-C-T

Variant names:

• chr18-20980393-C-T
• rs7227454
• NM_005406.3:c.2560-389G>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.2560-389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,060 control chromosomes in the GnomAD database, including 1,012 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 0.10 (1012 hom., cov: 32)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK1	NM_005406.3	c.2560-389G>A		intron_variant	Intron 21 of 32	ENST00000399799.3	NP_005397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK1	ENST00000399799.3	c.2560-389G>A		intron_variant	Intron 21 of 32	1	NM_005406.3	ENSP00000382697.1
ROCK1	ENST00000583556.1	n.22-389G>A		intron_variant	Intron 1 of 2	5
ROCK1	ENST00000635540.2	n.2560-389G>A		intron_variant	Intron 21 of 33	5		ENSP00000489185.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15490 AN: 151942 Hom.: 1008 Cov.: 32

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.102 AC: 15504 AN: 152060 Hom.: 1012 Cov.: 32 AF XY: 0.108 AC XY: 8025 AN XY: 74312

African (AFR) AF: 0.0555 AC: 2302 AN: 41476

American (AMR) AF: 0.180 AC: 2741 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0770 AC: 267 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1245 AN: 5170

South Asian (SAS) AF: 0.196 AC: 945 AN: 4816

European-Finnish (FIN) AF: 0.124 AC: 1311 AN: 10552

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6318 AN: 67998

Other (OTH) AF: 0.115 AC: 243 AN: 2110

Alfa AF: 0.0914 Hom.: 475

Bravo AF: 0.103

Asia WGS AF: 0.258 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-0.080
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: rs7227454; hg19: chr18-18560354;