chr18-112535-G-T

Variant names:

• chr18-112535-G-T
• rs9284390
• ENST00000608049.5:n.389+3082G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000608049.5(ROCK1P1):​n.389+3082G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00091 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROCK1P1 ENST00000608049.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 7 publications found

Genes affected

ROCK1P1 (HGNC:):

ROCK1P1 (HGNC:37832): (Rho associated coiled-coil containing protein kinase 1 pseudogene 1)

MIR8078 (HGNC:50102): (microRNA 8078) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK1P1	NR_160777.1	n.438G>T		non_coding_transcript_exon_variant	Exon 1 of 5
ROCK1P1	NR_033770.1	n.389+3082G>T		intron_variant	Intron 1 of 4
ROCK1P1	NR_160778.1	n.204+719G>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK1P1	ENST00000608049.5	n.389+3082G>T		intron_variant	Intron 1 of 4	1
ROCK1P1	ENST00000576266.7	n.472G>T		non_coding_transcript_exon_variant	Exon 1 of 5	4
ROCK1P1	ENST00000755797.1	n.91G>T		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.000899 AC: 90 AN: 100152 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000810

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000473

Gnomad SAS AF: 0.000299

Gnomad FIN AF: 0.00389

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000523

Gnomad OTH AF: 0.000709

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000152 AC: 58 AN: 381090 Hom.: 0 Cov.: 0 AF XY: 0.000124 AC XY: 26 AN XY: 209908

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000270 AC: 2 AN: 7402

American (AMR) AF: 0.00 AC: 0 AN: 22756

Ashkenazi Jewish (ASJ) AF: 0.0000876 AC: 1 AN: 11422

East Asian (EAS) AF: 0.000183 AC: 5 AN: 27342

South Asian (SAS) AF: 0.0000709 AC: 3 AN: 42334

European-Finnish (FIN) AF: 0.0000589 AC: 2 AN: 33974

Middle Eastern (MID) AF: 0.000746 AC: 1 AN: 1340

European-Non Finnish (NFE) AF: 0.000154 AC: 33 AN: 214662

Other (OTH) AF: 0.000554 AC: 11 AN: 19858

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000908 AC: 91 AN: 100228 Hom.: 0 Cov.: 30 AF XY: 0.000992 AC XY: 49 AN XY: 49398

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000850 AC: 20 AN: 23538

American (AMR) AF: 0.00109 AC: 12 AN: 11002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2158

East Asian (EAS) AF: 0.000474 AC: 2 AN: 4218

South Asian (SAS) AF: 0.000300 AC: 1 AN: 3336

European-Finnish (FIN) AF: 0.00389 AC: 31 AN: 7964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.000523 AC: 24 AN: 45858

Other (OTH) AF: 0.000697 AC: 1 AN: 1434

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 8579

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9284390; hg19: chr18-112535;