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18-21042578-G-A

Variant summary

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

The NM_005406.3(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
NM_005406.3 synonymous

Scores

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.11 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 955 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROCK1NM_005406.3 linkuse as main transcriptc.807C>T p.Tyr269= synonymous_variant 7/33 ENST00000399799.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK1ENST00000399799.3 linkuse as main transcriptc.807C>T p.Tyr269= synonymous_variant 7/331 NM_005406.3 P1
ROCK1ENST00000635540.2 linkuse as main transcriptc.807C>T p.Tyr269= synonymous_variant, NMD_transcript_variant 7/345

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00628
AC:
955
AN:
151998
Hom.:
6
Cov.:
32
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.:
9
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.:
70
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00628
AC:
955
AN:
152116
Hom.:
6
Cov.:
32
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.:
7
Bravo
AF:
0.00641
Asia WGS
AF:
0.00260
AC:
9
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022ROCK1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
11
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.

Other links and lift over

dbSNP: rs56085230; hg19: chr18-18622539; API