8-116866452-C-T

Variant names:

• chr8-116866452-C-T
• rs16889040
• NM_006265.3:c.144+134G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006265.3(RAD21):​c.144+134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 712,942 control chromosomes in the GnomAD database, including 28,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4454 hom., cov: 32)
  • Exomes 𝑓: 0.28 (23755 hom.)
• Consequence: RAD21 NM_006265.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.205
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Mungan syndrome

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-116866452-C-T is Benign according to our data. Variant chr8-116866452-C-T is described in ClinVar as Benign. ClinVar VariationId is 670486.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21	NM_006265.3	MANE Select	c.144+134G>A		intron	N/A	NP_006256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21	ENST00000297338.7	TSL:1 MANE Select	c.144+134G>A		intron	N/A	ENSP00000297338.2
	RAD21	ENST00000517749.2	TSL:1	c.144+134G>A		intron	N/A	ENSP00000430273.2
	RAD21	ENST00000517485.6	TSL:3	c.144+134G>A		intron	N/A	ENSP00000427923.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33170 AN: 151882 Hom.: 4453 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.281 AC: 157396 AN: 560942 Hom.: 23755 AF XY: 0.287 AC XY: 82017 AN XY: 286244

African (AFR) AF: 0.0591 AC: 813 AN: 13762

American (AMR) AF: 0.205 AC: 2873 AN: 14032

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 2616 AN: 13594

East Asian (EAS) AF: 0.132 AC: 3933 AN: 29732

South Asian (SAS) AF: 0.469 AC: 15339 AN: 32686

European-Finnish (FIN) AF: 0.333 AC: 9563 AN: 28754

Middle Eastern (MID) AF: 0.232 AC: 491 AN: 2114

European-Non Finnish (NFE) AF: 0.288 AC: 114568 AN: 397372

Other (OTH) AF: 0.249 AC: 7200 AN: 28896

GnomAD4 genome AF: 0.218 AC: 33181 AN: 152000 Hom.: 4454 Cov.: 32 AF XY: 0.224 AC XY: 16663 AN XY: 74310

African (AFR) AF: 0.0619 AC: 2569 AN: 41502

American (AMR) AF: 0.191 AC: 2913 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3472

East Asian (EAS) AF: 0.151 AC: 785 AN: 5186

South Asian (SAS) AF: 0.473 AC: 2284 AN: 4824

European-Finnish (FIN) AF: 0.330 AC: 3473 AN: 10530

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

European-Non Finnish (NFE) AF: 0.289 AC: 19631 AN: 67932

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.245 Hom.: 655

Bravo AF: 0.197

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.35
PhyloP100		-0.20
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: rs16889040; hg19: chr8-117878691;