Genetic Variant ROCK1:c.-895C>T (chr18-21111805-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005406.3(ROCK1):c.-895C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,974 control chromosomes in the GnomAD database, including 3,772 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 0.15 ( 3771 hom., cov: 30)

Exomes 𝑓: 0.043 ( 1 hom. )

Consequence

ROCK1
NM_005406.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Publications

12 publications found

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:

ENSG00000308413 (HGNC:):

ENSG00000308413 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005406.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	NM_005406.3	MANE Select	c.-895C>T		5_prime_UTR	Exon 1 of 33	NP_005397.1	Q13464

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROCK1	ENST00000399799.3	TSL:1 MANE Select	c.-895C>T	5_prime_UTR	Exon 1 of 33	ENSP00000382697.1	Q13464
ENSG00000308413	ENST00000833852.1		n.132-469G>A	intron	N/A
ENSG00000308413	ENST00000833853.1		n.225-432G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22850

AN:

151704

Hom.:

3757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.0844

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.0226

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.0432

AC:

AN:

162

Hom.:

Cov.:

AF XY:

0.0397

AC XY:

AN XY:

126

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0429

AC:

AN:

140

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.151

AC:

22927

AN:

151812

Hom.:

3771

Cov.:

AF XY:

0.148

AC XY:

10992

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.404

AC:

16671

AN:

41302

American (AMR)

AF:

0.172

AC:

2626

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

244

AN:

3472

East Asian (EAS)

AF:

0.0851

AC:

434

AN:

5100

South Asian (SAS)

AF:

0.0342

AC:

165

AN:

4820

European-Finnish (FIN)

AF:

0.0226

AC:

240

AN:

10602

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0328

AC:

2230

AN:

67930

Other (OTH)

AF:

0.129

AC:

272

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

764

1528

2293

3057

3821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0709

Hom.:

4439

Bravo

AF:

0.175

Asia WGS

AF:

0.0880

AC:

306

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

2.0

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=296/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over