rs17202375

Variant names:

• chr18-21041312-A-G
• rs17202375
• NM_005406.3:c.959+785T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005406.3(ROCK1):​c.959+785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 150,994 control chromosomes in the GnomAD database, including 417 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 0.062 (417 hom., cov: 30)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• Publications: 10 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0856 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	NM_005406.3	MANE Select	c.959+785T>C		intron	N/A	NP_005397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	ENST00000399799.3	TSL:1 MANE Select	c.959+785T>C		intron	N/A	ENSP00000382697.1
	ROCK1	ENST00000635540.2	TSL:5	n.959+785T>C		intron	N/A	ENSP00000489185.1

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9372 AN: 150882 Hom.: 417 Cov.: 30

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0606

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0886

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.0710

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0620 AC: 9367 AN: 150994 Hom.: 417 Cov.: 30 AF XY: 0.0637 AC XY: 4696 AN XY: 73734

African (AFR) AF: 0.0136 AC: 562 AN: 41334

American (AMR) AF: 0.0557 AC: 845 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.0886 AC: 306 AN: 3454

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0255 AC: 122 AN: 4784

European-Finnish (FIN) AF: 0.137 AC: 1378 AN: 10030

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0875 AC: 5925 AN: 67750

Other (OTH) AF: 0.0703 AC: 147 AN: 2092

Alfa AF: 0.0794 Hom.: 860

Bravo AF: 0.0549

Asia WGS AF: 0.0130 AC: 44 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.35
DANN	Benign	0.74
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17202375; hg19: chr18-18621273;