18-20980393-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005406.3(ROCK1):​c.2560-389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,060 control chromosomes in the GnomAD database, including 1,012 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 0.10 ( 1012 hom., cov: 32)

Consequence

ROCK1
NM_005406.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0800
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ROCK1NM_005406.3 linkc.2560-389G>A intron_variant Intron 21 of 32 ENST00000399799.3 NP_005397.1 Q13464

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ROCK1ENST00000399799.3 linkc.2560-389G>A intron_variant Intron 21 of 32 1 NM_005406.3 ENSP00000382697.1 Q13464
ROCK1ENST00000583556.1 linkn.22-389G>A intron_variant Intron 1 of 2 5
ROCK1ENST00000635540.2 linkn.2560-389G>A intron_variant Intron 21 of 33 5 ENSP00000489185.1 A0A0U1RQV4

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15490
AN:
151942
Hom.:
1008
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0556
Gnomad AMI
AF:
0.110
Gnomad AMR
AF:
0.180
Gnomad ASJ
AF:
0.0770
Gnomad EAS
AF:
0.242
Gnomad SAS
AF:
0.197
Gnomad FIN
AF:
0.124
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.0928
Gnomad OTH
AF:
0.109
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.102
AC:
15504
AN:
152060
Hom.:
1012
Cov.:
32
AF XY:
0.108
AC XY:
8025
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0555
Gnomad4 AMR
AF:
0.180
Gnomad4 ASJ
AF:
0.0770
Gnomad4 EAS
AF:
0.241
Gnomad4 SAS
AF:
0.196
Gnomad4 FIN
AF:
0.124
Gnomad4 NFE
AF:
0.0929
Gnomad4 OTH
AF:
0.115
Alfa
AF:
0.0908
Hom.:
419
Bravo
AF:
0.103
Asia WGS
AF:
0.258
AC:
895
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.9
DANN
Benign
0.69

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: rs7227454; hg19: chr18-18560354; API