chr8-116857221-A-G

Variant names:

• chr8-116857221-A-G
• rs16888927
• NM_006265.3:c.688+46T>C

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.688+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,525,326 control chromosomes in the GnomAD database, including 64,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4466 hom., cov: 33)
  • Exomes 𝑓: 0.29 (60482 hom.)
• Consequence: RAD21 NM_006265.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0830
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-116857221-A-G is Benign according to our data. Variant chr8-116857221-A-G is described in ClinVar as Benign. ClinVar VariationId is 675063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 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.688+46T>C		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.688+46T>C		intron	N/A	ENSP00000297338.2	O60216
	RAD21	ENST00000517749.2	TSL:1	c.688+46T>C		intron	N/A	ENSP00000430273.2	O60216
	RAD21	ENST00000517485.6	TSL:3	c.688+46T>C		intron	N/A	ENSP00000427923.2	O60216

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33206 AN: 152064 Hom.: 4465 Cov.: 33

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.274 AC: 64022 AN: 233322 AF XY: 0.290

Gnomad AFR exome AF: 0.0589

Gnomad AMR exome AF: 0.225

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.288 AC: 395024 AN: 1373142 Hom.: 60482 Cov.: 21 AF XY: 0.294 AC XY: 201279 AN XY: 684472

African (AFR) AF: 0.0566 AC: 1748 AN: 30906

American (AMR) AF: 0.222 AC: 9350 AN: 42088

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 4731 AN: 24280

East Asian (EAS) AF: 0.136 AC: 5313 AN: 38982

South Asian (SAS) AF: 0.474 AC: 38527 AN: 81246

European-Finnish (FIN) AF: 0.330 AC: 16713 AN: 50614

Middle Eastern (MID) AF: 0.241 AC: 937 AN: 3884

European-Non Finnish (NFE) AF: 0.290 AC: 302881 AN: 1044150

Other (OTH) AF: 0.260 AC: 14824 AN: 56992

GnomAD4 genome AF: 0.218 AC: 33217 AN: 152184 Hom.: 4466 Cov.: 33 AF XY: 0.224 AC XY: 16675 AN XY: 74386

African (AFR) AF: 0.0619 AC: 2574 AN: 41562

American (AMR) AF: 0.192 AC: 2928 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3470

East Asian (EAS) AF: 0.151 AC: 783 AN: 5178

South Asian (SAS) AF: 0.473 AC: 2278 AN: 4820

European-Finnish (FIN) AF: 0.330 AC: 3484 AN: 10570

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

European-Non Finnish (NFE) AF: 0.289 AC: 19644 AN: 67988

Other (OTH) AF: 0.210 AC: 444 AN: 2114

Alfa AF: 0.249 Hom.: 1628

Bravo AF: 0.197

Asia WGS AF: 0.306 AC: 1066 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.76
PhyloP100		0.083
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: rs16888927; hg19: chr8-117869460;