rs970084

Positions:

• chr20-1240527-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384355.1(RAD21L1):​c.856+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,448,594 control chromosomes in the GnomAD database, including 23,317 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 0.15 (1975 hom., cov: 32)
  • Exomes 𝑓: 0.18 (21342 hom.)
• Consequence: RAD21L1 NM_001384355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

Genes affected

RAD21L1 (HGNC:16271): (RAD21 cohesin complex component like 1) Predicted to enable chromatin binding activity. Predicted to be involved in mitotic sister chromatid cohesion; replication-born double-strand break repair via sister chromatid exchange; and synaptonemal complex assembly. Predicted to act upstream of or within several processes, including double-strand break repair via homologous recombination; homologous chromosome segregation; and seminiferous tubule development. Predicted to be located in lateral element. Predicted to be part of nuclear meiotic cohesin complex and nuclear mitotic cohesin complex. Predicted to be active in synaptonemal complex. [provided by Alliance of Genome Resources, Apr 2022]

RAD21L1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD21L1	NM_001384355.1	c.856+93G>A		intron_variant		ENST00000683101.1	NP_001371284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD21L1	ENST00000683101.1	c.856+93G>A		intron_variant			NM_001384355.1	ENSP00000507397.1
RAD21L1	ENST00000409241.5	c.856+93G>A		intron_variant		1		ENSP00000386414.1
RAD21L1	ENST00000402452.5	c.856+93G>A		intron_variant		5		ENSP00000385925.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23108 AN: 152034 Hom.: 1975 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.177 AC: 229000 AN: 1296442 Hom.: 21342 AF XY: 0.176 AC XY: 111753 AN XY: 634854

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.0130

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.152 AC: 23115 AN: 152152 Hom.: 1975 Cov.: 32 AF XY: 0.150 AC XY: 11164 AN XY: 74380

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0200

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.167

Alfa AF: 0.180 Hom.: 1462

Bravo AF: 0.147

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.64

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: rs970084; hg19: chr20-1221171;