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GeneBe

18-21006451-A-C

Variant summary

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

The NM_005406.3(ROCK1):c.1785T>G(p.Ser595=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,613,752 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0041 ( 26 hom. )

Consequence

ROCK1
NM_005406.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.292
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=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-21006451-A-C is Benign according to our data. Variant chr18-21006451-A-C is described in ClinVar as [Benign]. Clinvar id is 711996.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=0.292 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 542 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROCK1NM_005406.3 linkuse as main transcriptc.1785T>G p.Ser595= synonymous_variant 16/33 ENST00000399799.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK1ENST00000399799.3 linkuse as main transcriptc.1785T>G p.Ser595= synonymous_variant 16/331 NM_005406.3 P1
ROCK1ENST00000635540.2 linkuse as main transcriptc.1785T>G p.Ser595= synonymous_variant, NMD_transcript_variant 16/345

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00356
AC:
542
AN:
152174
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000628
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00353
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0202
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00351
Gnomad OTH
AF:
0.00334
GnomAD3 exomes
AF:
0.00360
AC:
905
AN:
251156
Hom.:
4
AF XY:
0.00358
AC XY:
486
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.00147
Gnomad ASJ exome
AF:
0.000496
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000719
Gnomad FIN exome
AF:
0.0180
Gnomad NFE exome
AF:
0.00351
Gnomad OTH exome
AF:
0.00457
GnomAD4 exome
AF:
0.00408
AC:
5958
AN:
1461460
Hom.:
26
Cov.:
31
AF XY:
0.00389
AC XY:
2827
AN XY:
727030
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.00161
Gnomad4 ASJ exome
AF:
0.000651
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000777
Gnomad4 FIN exome
AF:
0.0177
Gnomad4 NFE exome
AF:
0.00413
Gnomad4 OTH exome
AF:
0.00421
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00356
AC:
542
AN:
152292
Hom.:
3
Cov.:
32
AF XY:
0.00423
AC XY:
315
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000626
Gnomad4 AMR
AF:
0.00353
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0202
Gnomad4 NFE
AF:
0.00351
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00285
Hom.:
0
Bravo
AF:
0.00240
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00338
EpiControl
AF:
0.00367

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
6.3
Dann
Benign
0.65

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

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

Other links and lift over

dbSNP: rs112165707; hg19: chr18-18586412; COSMIC: COSV67695027; API