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GeneBe

18-20970392-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005406.3(ROCK1):c.2776A>C(p.Arg926=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,614,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

ROCK1
NM_005406.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.87
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 -9 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=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-20970392-T-G is Benign according to our data. Variant chr18-20970392-T-G is described in ClinVar as [Benign]. Clinvar id is 769935.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=1.87 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 276 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROCK1NM_005406.3 linkuse as main transcriptc.2776A>C p.Arg926= synonymous_variant 23/33 ENST00000399799.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK1ENST00000399799.3 linkuse as main transcriptc.2776A>C p.Arg926= synonymous_variant 23/331 NM_005406.3 P1
ROCK1ENST00000583556.1 linkuse as main transcriptn.238A>C non_coding_transcript_exon_variant 3/35
ROCK1ENST00000635540.2 linkuse as main transcriptc.2776A>C p.Arg926= synonymous_variant, NMD_transcript_variant 23/345

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00181
AC:
276
AN:
152236
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00511
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00334
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000533
AC:
134
AN:
251214
Hom.:
1
AF XY:
0.000346
AC XY:
47
AN XY:
135760
show subpopulations
Gnomad AFR exome
AF:
0.00566
Gnomad AMR exome
AF:
0.000809
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000257
AC:
375
AN:
1461654
Hom.:
0
Cov.:
30
AF XY:
0.000219
AC XY:
159
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00639
Gnomad4 AMR exome
AF:
0.00101
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000567
Gnomad4 OTH exome
AF:
0.000729
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00181
AC:
275
AN:
152354
Hom.:
1
Cov.:
32
AF XY:
0.00165
AC XY:
123
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00508
Gnomad4 AMR
AF:
0.00333
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000733
Hom.:
0
Bravo
AF:
0.00226
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

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 testingInvitaeJun 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
13
Dann
Benign
0.70

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: rs45533032; hg19: chr18-18550353; API