rs11874761

Positions:

• chr18-21111805-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK1	NM_005406.3	c.-895C>T		5_prime_UTR_variant	1/33	ENST00000399799.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK1	ENST00000399799.3	c.-895C>T		5_prime_UTR_variant	1/33	1	NM_005406.3	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22850 AN: 151704 Hom.: 3757 Cov.: 30

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: 7 AN: 162 Hom.: 1 Cov.: 0 AF XY: 0.0397 AC XY: 5 AN XY: 126

Gnomad4 AFR exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.151 AC: 22927 AN: 151812 Hom.: 3771 Cov.: 30 AF XY: 0.148 AC XY: 10992 AN XY: 74192

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.0851

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.0328

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0531 Hom.: 901

Bravo AF: 0.175

Asia WGS AF: 0.0880 AC: 306 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	17
DANN	Benign	0.83

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: rs11874761; hg19: chr18-18691766;