8-116874629-T-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21	NM_006265.3	c.-51A>T		5_prime_UTR_variant	Exon 1 of 14	ENST00000297338.7	NP_006256.1
RAD21-AS1	NR_033886.1	n.206T>A		non_coding_transcript_exon_variant	Exon 1 of 2
MIR3610	NR_037404.1	n.*99A>T		downstream_gene_variant
MIR3610	unassigned_transcript_1519	n.*111A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7	c.-51A>T		5_prime_UTR_variant	Exon 1 of 14	1	NM_006265.3	ENSP00000297338.2

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

Gnomad4 AFR exome AF: 0.0496

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.00215

Gnomad4 SAS exome AF: 0.0315

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0210

Gnomad4 OTH exome AF: 0.0287

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0664

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0830

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0135 Hom.: 1

Bravo AF: 0.0303

Asia WGS AF: 0.0220 AC: 77 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Apr 28, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.92
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

Publications

LitVar

Other links and lift over

dbSNP: rs16889189; hg19: chr8-117886868;