chr8-116847501-T-C

Variant names:

• chr8-116847501-T-C
• rs1315026169
• NM_006265.3:c.1895A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_006265.3(RAD21):​c.1895A>G​(p.Ter632Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RAD21 NM_006265.3 stop_retained
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.33
• Publications: 0 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]

UTP23 (HGNC:28224): (UTP23 small subunit processome component) Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Predicted to be involved in rRNA processing. Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. Implicated in colorectal adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

LOC112268030 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 8-116847501-T-C is Benign according to our data. Variant chr8-116847501-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1991742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.33 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00000275 (4/1453516) while in subpopulation AMR AF = 0.0000694 (3/43226). AF 95% confidence interval is 0.0000184. There are 0 homozygotes in GnomAdExome4. There are 3 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

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.1895A>G	p.Ter632Ter	stop_retained	Exon 14 of 14	NP_006256.1	O60216

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21	ENST00000297338.7	TSL:1 MANE Select	c.1895A>G	p.Ter632Ter	stop_retained	Exon 14 of 14	ENSP00000297338.2	O60216
	RAD21	ENST00000517749.2	TSL:1	c.1895A>G	p.Ter632Ter	stop_retained	Exon 14 of 14	ENSP00000430273.2	O60216
	RAD21	ENST00000517485.6	TSL:3	c.1895A>G	p.Ter632Ter	stop_retained	Exon 14 of 14	ENSP00000427923.2	O60216

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000818 AC: 2 AN: 244604 AF XY: 0.00000757

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000605

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453516 Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3 AN XY: 722600

African (AFR) AF: 0.00 AC: 0 AN: 32888

American (AMR) AF: 0.0000694 AC: 3 AN: 43226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25684

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 84906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108426

Other (OTH) AF: 0.00 AC: 0 AN: 59948

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cornelia de Lange syndrome 4 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1315026169; hg19: chr8-117859740;