rs970084

Variant names:

• chr20-1240527-G-A
• rs970084
• NM_001384355.1:c.856+93G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAD21L1	NM_001384355.1	c.856+93G>A		intron_variant	Intron 8 of 13	ENST00000683101.1	NP_001371284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21L1	ENST00000683101.1	c.856+93G>A		intron_variant	Intron 8 of 13		NM_001384355.1	ENSP00000507397.1
RAD21L1	ENST00000409241.5	c.856+93G>A		intron_variant	Intron 8 of 13	1		ENSP00000386414.1
RAD21L1	ENST00000402452.5	c.856+93G>A		intron_variant	Intron 8 of 13	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

African (AFR) AF: 0.103 AC: 2784 AN: 27156

American (AMR) AF: 0.130 AC: 2392 AN: 18468

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 5093 AN: 20920

East Asian (EAS) AF: 0.0130 AC: 424 AN: 32622

South Asian (SAS) AF: 0.135 AC: 8362 AN: 62048

European-Finnish (FIN) AF: 0.166 AC: 6739 AN: 40510

Middle Eastern (MID) AF: 0.227 AC: 903 AN: 3978

European-Non Finnish (NFE) AF: 0.186 AC: 192948 AN: 1037238

Other (OTH) AF: 0.175 AC: 9355 AN: 53502

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

African (AFR) AF: 0.101 AC: 4186 AN: 41508

American (AMR) AF: 0.156 AC: 2383 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 854 AN: 3464

East Asian (EAS) AF: 0.0200 AC: 104 AN: 5188

South Asian (SAS) AF: 0.127 AC: 614 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1799 AN: 10566

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12666 AN: 68002

Other (OTH) AF: 0.167 AC: 354 AN: 2114

Alfa AF: 0.175 Hom.: 2579

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
PhyloP100		-0.21
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: rs970084; hg19: chr20-1221171;