8-116874629-T-C

Variant names:

• chr8-116874629-T-C
• rs16889189
• NM_006265.3:c.-51A>G

Variant summary

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

The NM_006265.3(RAD21):​c.-51A>G variant causes a 5 prime UTR 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 0.000016 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RAD21 NM_006265.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 2 publications found

Genes affected

RAD21 (HGNC:9811): (RAD21 cohesin complex component) The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells. [provided by RefSeq, Jul 2008]

RAD21-AS1 (HGNC:32158): (RAD21 antisense RNA 1)

MIR3610 (HGNC:38942): (microRNA 3610) 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=-0.58).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006265.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21	NM_006265.3	MANE Select	c.-51A>G		5_prime_UTR	Exon 1 of 14	NP_006256.1	O60216
	RAD21-AS1	NR_033886.1		n.206T>C		non_coding_transcript_exon	Exon 1 of 2
	MIR3610	NR_037404.1		n.*99A>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21	ENST00000297338.7	TSL:1 MANE Select	c.-51A>G		5_prime_UTR	Exon 1 of 14	ENSP00000297338.2	O60216
	RAD21-AS1	ENST00000521487.2	TSL:1	n.206T>C		non_coding_transcript_exon	Exon 1 of 2
	RAD21	ENST00000927340.1		c.-86A>G		5_prime_UTR	Exon 1 of 14	ENSP00000597399.1

Frequencies

GnomAD3 genomes AF: 0.0000162 AC: 1 AN: 61892 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000142 AC: 3 AN: 210868 Hom.: 0 Cov.: 0 AF XY: 0.00000851 AC XY: 1 AN XY: 117548

African (AFR) AF: 0.00 AC: 0 AN: 5406

American (AMR) AF: 0.00 AC: 0 AN: 12336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4744

East Asian (EAS) AF: 0.000119 AC: 1 AN: 8380

South Asian (SAS) AF: 0.0000225 AC: 1 AN: 44500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 700

European-Non Finnish (NFE) AF: 0.00000863 AC: 1 AN: 115850

Other (OTH) AF: 0.00 AC: 0 AN: 10052

GnomAD4 genome AF: 0.0000162 AC: 1 AN: 61892 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 28372

African (AFR) AF: 0.00 AC: 0 AN: 16346

American (AMR) AF: 0.00 AC: 0 AN: 4646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1702

East Asian (EAS) AF: 0.000578 AC: 1 AN: 1730

South Asian (SAS) AF: 0.00 AC: 0 AN: 1728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31432

Other (OTH) AF: 0.00 AC: 0 AN: 836

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		-0.15
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs16889189; hg19: chr8-117886868;