rs7239317

Positions:

• chr18-21030106-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005406.3(ROCK1):​c.1052-1171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,194 control chromosomes in the GnomAD database, including 606 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 0.074 (606 hom., cov: 32)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROCK1	NM_005406.3	c.1052-1171G>A		intron_variant		ENST00000399799.3	NP_005397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROCK1	ENST00000399799.3	c.1052-1171G>A		intron_variant		1	NM_005406.3	ENSP00000382697	P1
ROCK1	ENST00000635540.2	c.1052-1171G>A		intron_variant, NMD_transcript_variant		5		ENSP00000489185

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11253 AN: 152076 Hom.: 603 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0967

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0782

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

GnomAD4 genome AF: 0.0741 AC: 11276 AN: 152194 Hom.: 606 Cov.: 32 AF XY: 0.0747 AC XY: 5559 AN XY: 74414

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0967

Gnomad4 EAS AF: 0.0869

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.0788

Alfa AF: 0.0516 Hom.: 153

Bravo AF: 0.0851

Asia WGS AF: 0.0740 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
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

Other links and lift over

dbSNP: rs7239317; hg19: chr18-18610067;