Variant 18-21039464-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005406.3(ROCK1):c.1051+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,592,280 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 21 hom. )

Consequence

ROCK1
NM_005406.3 splice_region, intron

Scores

Splicing: ADA: 0.0003838

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 18-21039464-A-G is Benign according to our data. Variant chr18-21039464-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 784748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 407 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK1	NM_005406.3 linkuse as main transcript	c.1051+8T>C		splice_region_variant, intron_variant		ENST00000399799.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK1	ENST00000399799.3 linkuse as main transcript	c.1051+8T>C		splice_region_variant, intron_variant		1	NM_005406.3	P1
ROCK1	ENST00000635540.2 linkuse as main transcript	c.1051+8T>C		splice_region_variant, intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

408

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00257

AC:

605

AN:

235196

Hom.:

AF XY:

0.00279

AC XY:

355

AN XY:

127366

show subpopulations

Gnomad AFR exome

AF:

0.000756

Gnomad AMR exome

AF:

0.000786

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00182

Gnomad FIN exome

AF:

0.000610

Gnomad NFE exome

AF:

0.00449

Gnomad OTH exome

AF:

0.00304

GnomAD4 exome

AF:

0.00429

AC:

6179

AN:

1440004

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3053

AN XY:

716880

show subpopulations

Gnomad4 AFR exome

AF:

0.000785

Gnomad4 AMR exome

AF:

0.000873

Gnomad4 ASJ exome

AF:

0.0000785

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00164

Gnomad4 FIN exome

AF:

0.000809

Gnomad4 NFE exome

AF:

0.00521

Gnomad4 OTH exome

AF:

0.00320

GnomAD4 genome

AF:

0.00267

AC:

407

AN:

152276

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00467

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00242

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	ROCK1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.24

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00038

dbscSNV1_RF

Benign

0.018

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.

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