chr18-21073649-C-T

Position:

• chr18-21073649-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK1	NM_005406.3	c.94-3036G>A		intron_variant		ENST00000399799.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK1	ENST00000399799.3	c.94-3036G>A		intron_variant		1	NM_005406.3	P1
ROCK1	ENST00000635540.2	c.94-3036G>A		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.470

Alfa AF: 0.536 Hom.: 16595

Bravo AF: 0.438

Asia WGS AF: 0.419 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.77

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: rs2127958; hg19: chr18-18653610;