Variant 18-21042578-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000399799.3(ROCK1):c.807C>T(p.Tyr269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 1,613,496 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 70 hom. )

Consequence

ROCK1
ENST00000399799.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.11

Variant links:

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]

ROCK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 18-21042578-G-A is Benign according to our data. Variant chr18-21042578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648612.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.11 with no splicing effect.

BS2

High AC in GnomAd4 at 955 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROCK1	NM_005406.3 linkuse as main transcript	c.807C>T	p.Tyr269=	synonymous_variant	7/33	ENST00000399799.3	NP_005397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROCK1	ENST00000399799.3 linkuse as main transcript	c.807C>T	p.Tyr269=	synonymous_variant	7/33	1	NM_005406.3	ENSP00000382697	P1
ROCK1	ENST00000635540.2 linkuse as main transcript	c.807C>T	p.Tyr269=	synonymous_variant, NMD_transcript_variant	7/34	5		ENSP00000489185

Frequencies

GnomAD3 genomes

AF:

0.00628

AC:

955

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00614

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00940

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00669

AC:

1680

AN:

251170

Hom.:

AF XY:

0.00698

AC XY:

948

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00379

Gnomad FIN exome

AF:

0.00490

Gnomad NFE exome

AF:

0.00982

Gnomad OTH exome

AF:

0.00816

GnomAD4 exome

AF:

0.00815

AC:

11907

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00818

AC XY:

5948

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00474

Gnomad4 FIN exome

AF:

0.00468

Gnomad4 NFE exome

AF:

0.00909

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.00628

AC:

955

AN:

152116

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

431

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00570

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00614

Gnomad4 NFE

AF:

0.00940

Gnomad4 OTH

AF:

0.00854

Alfa

AF:

0.00795

Hom.:

Bravo

AF:

0.00641

Asia WGS

AF:

0.00260

AC:

AN:

3476

EpiCase

AF:

0.0104

EpiControl

AF:

0.0112

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ROCK1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over