8-116874629-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006265.3(RAD21):​c.-51A>T 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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (89 hom., cov: 15)
  • Exomes 𝑓: 0.024 (97 hom.)
• Consequence: RAD21 NM_006265.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 8-116874629-T-A is Benign according to our data. Variant chr8-116874629-T-A is described in ClinVar as Benign. ClinVar VariationId is 516238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

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>T		5_prime_UTR	Exon 1 of 14	NP_006256.1	O60216
	RAD21-AS1	NR_033886.1		n.206T>A		non_coding_transcript_exon	Exon 1 of 2
	MIR3610	NR_037404.1		n.*99A>T		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>T		5_prime_UTR	Exon 1 of 14	ENSP00000297338.2	O60216
	RAD21-AS1	ENST00000521487.2	TSL:1	n.206T>A		non_coding_transcript_exon	Exon 1 of 2
	RAD21	ENST00000927340.1		c.-86A>T		5_prime_UTR	Exon 1 of 14	ENSP00000597399.1

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 4311 AN: 61856 Hom.: 88 Cov.: 15

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.0238 AC: 5019 AN: 210832 Hom.: 97 Cov.: 0 AF XY: 0.0247 AC XY: 2902 AN XY: 117522

African (AFR) AF: 0.0496 AC: 268 AN: 5404

American (AMR) AF: 0.0160 AC: 197 AN: 12334

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 231 AN: 4742

East Asian (EAS) AF: 0.00215 AC: 18 AN: 8380

South Asian (SAS) AF: 0.0315 AC: 1403 AN: 44492

European-Finnish (FIN) AF: 0.0149 AC: 133 AN: 8900

Middle Eastern (MID) AF: 0.0671 AC: 47 AN: 700

European-Non Finnish (NFE) AF: 0.0210 AC: 2434 AN: 115832

Other (OTH) AF: 0.0287 AC: 288 AN: 10048

GnomAD4 genome AF: 0.0697 AC: 4318 AN: 61926 Hom.: 89 Cov.: 15 AF XY: 0.0726 AC XY: 2063 AN XY: 28412

African (AFR) AF: 0.123 AC: 2011 AN: 16378

American (AMR) AF: 0.0664 AC: 309 AN: 4656

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 186 AN: 1702

East Asian (EAS) AF: 0.00463 AC: 8 AN: 1728

South Asian (SAS) AF: 0.0830 AC: 144 AN: 1734

European-Finnish (FIN) AF: 0.0342 AC: 97 AN: 2836

Middle Eastern (MID) AF: 0.196 AC: 22 AN: 112

European-Non Finnish (NFE) AF: 0.0453 AC: 1422 AN: 31424

Other (OTH) AF: 0.0758 AC: 64 AN: 844

Alfa AF: 0.0135 Hom.: 1

Bravo AF: 0.0303

Asia WGS AF: 0.0220 AC: 77 AN: 3456

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs16889189; hg19: chr8-117886868;