18-21111805-G-A

Variant names:

• chr18-21111805-G-A
• rs11874761
• NM_005406.3:c.-895C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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]

ENSG00000308413 (HGNC:):

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 (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

Selected	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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK1	ENST00000399799.3	TSL:1 MANE Select	c.-895C>T		5_prime_UTR	Exon 1 of 33	ENSP00000382697.1
	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.: 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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0429 AC: 6 AN: 140

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

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: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0328 AC: 2230 AN: 67930

Other (OTH) AF: 0.129 AC: 272 AN: 2110

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	17
DANN	Benign	0.83
PhyloP100		2.0
PromoterAI		0.029	Neutral
Mutation Taster		=296/4	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: rs11874761; hg19: chr18-18691766;