8-116852713-TAAAAA-TAAA

Variant names:

• chr8-116852713-TAA-T
• rs369816312
• NM_006265.3:c.1162-7_1162-6delTT

Variant summary

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

The NM_006265.3(RAD21):​c.1162-7_1162-6delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000461 in 1,173,490 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00052 (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 = 0.000519 (539/1038192) while in subpopulation SAS AF= 0.0017 (74/43406). AF 95% confidence interval is 0.00139. There are 0 homozygotes in gnomad4_exome. There are 297 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000148 AC: 2 AN: 135298 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000265

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00155 AC: 135 AN: 87152 Hom.: 0 AF XY: 0.00178 AC XY: 86 AN XY: 48372

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00369

Gnomad EAS exome AF: 0.00162

Gnomad SAS exome AF: 0.00213

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.000519 AC: 539 AN: 1038192 Hom.: 0 AF XY: 0.000582 AC XY: 297 AN XY: 510516

Gnomad4 AFR exome AF: 0.000495

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00137

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.00170

Gnomad4 FIN exome AF: 0.000739

Gnomad4 NFE exome AF: 0.000416

Gnomad4 OTH exome AF: 0.000638

GnomAD4 genome AF: 0.0000148 AC: 2 AN: 135298 Hom.: 0 Cov.: 31 AF XY: 0.0000307 AC XY: 2 AN XY: 65204

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000265

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs369816312; hg19: chr8-117864952;