chr8-116852713-T-TAAA

Variant names:

• chr8-116852713-T-TAAA
• rs369816312
• NM_006265.3:c.1162-8_1162-6dupTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_006265.3(RAD21):​c.1162-8_1162-6dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000652 in 1,043,296 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: RAD21 NM_006265.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000652 (68/1043296) while in subpopulation SAS AF= 0.000229 (10/43698). AF 95% confidence interval is 0.000123. There are 0 homozygotes in gnomad4_exome. There are 32 alleles in male gnomad4_exome subpopulation. Median coverage is 2. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21	NM_006265.3	c.1162-8_1162-6dupTTT		splice_region_variant, intron_variant	Intron 9 of 13	ENST00000297338.7	NP_006256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7	c.1162-8_1162-6dupTTT		splice_region_variant, intron_variant	Intron 9 of 13	1	NM_006265.3	ENSP00000297338.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000574 AC: 5 AN: 87152 Hom.: 0 AF XY: 0.0000413 AC XY: 2 AN XY: 48372

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000180

Gnomad SAS exome AF: 0.000106

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000676

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000652 AC: 68 AN: 1043296 Hom.: 0 Cov.: 2 AF XY: 0.0000624 AC XY: 32 AN XY: 513034

Gnomad4 AFR exome AF: 0.0000448

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000229

Gnomad4 FIN exome AF: 0.000136

Gnomad4 NFE exome AF: 0.0000578

Gnomad4 OTH exome AF: 0.0000470

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs369816312; hg19: chr8-117864952;