rs16888997

Variant names:

• chr8-116864169-C-T
• rs16888997
• NM_006265.3:c.145-910G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006265.3(RAD21):​c.145-910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,712 control chromosomes in the GnomAD database, including 4,461 homozygotes. 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 0.22 (4461 hom., cov: 31)
• Consequence: RAD21 NM_006265.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 5 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 Gene-Disease associations (from GenCC):

• Cornelia de Lange syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Cornelia de Lange syndrome 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Mungan syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.458 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.145-910G>A		intron	N/A	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.145-910G>A		intron	N/A	ENSP00000297338.2	O60216
	RAD21	ENST00000517749.2	TSL:1	c.145-910G>A		intron	N/A	ENSP00000430273.2	O60216
	RAD21	ENST00000517485.6	TSL:3	c.145-910G>A		intron	N/A	ENSP00000427923.2	O60216

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33155 AN: 151594 Hom.: 4460 Cov.: 31

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 33166 AN: 151712 Hom.: 4461 Cov.: 31 AF XY: 0.224 AC XY: 16641 AN XY: 74130

African (AFR) AF: 0.0621 AC: 2568 AN: 41378

American (AMR) AF: 0.191 AC: 2909 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3464

East Asian (EAS) AF: 0.151 AC: 776 AN: 5148

South Asian (SAS) AF: 0.475 AC: 2276 AN: 4796

European-Finnish (FIN) AF: 0.331 AC: 3479 AN: 10498

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19636 AN: 67910

Other (OTH) AF: 0.210 AC: 442 AN: 2108

Alfa AF: 0.245 Hom.: 655

Bravo AF: 0.197

Asia WGS AF: 0.306 AC: 1062 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.18
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs16888997; hg19: chr8-117876408;