20-1253746-G-A

Variant names:

• chr20-1253746-G-A
• rs10485821
• NM_001384355.1:c.1480-523G>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.1480-523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 152,260 control chromosomes in the GnomAD database, including 383 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 0.061 (383 hom., cov: 32)
• Consequence: RAD21L1 NM_001384355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384355.1. 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
	RAD21L1	NM_001384355.1	MANE Select	c.1480-523G>A		intron	N/A	NP_001371284.1
	RAD21L1	NM_001136566.3		c.1483-523G>A		intron	N/A	NP_001130038.2
	RAD21L1	NM_001384356.1		c.1006-523G>A		intron	N/A	NP_001371285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21L1	ENST00000683101.1	MANE Select	c.1480-523G>A		intron	N/A	ENSP00000507397.1
	RAD21L1	ENST00000409241.5	TSL:1	c.1483-523G>A		intron	N/A	ENSP00000386414.1
	RAD21L1	ENST00000402452.5	TSL:5	c.1386+5043G>A		intron	N/A	ENSP00000385925.1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9243 AN: 152142 Hom.: 381 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.0521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0607 AC: 9243 AN: 152260 Hom.: 383 Cov.: 32 AF XY: 0.0589 AC XY: 4386 AN XY: 74432

African (AFR) AF: 0.0180 AC: 749 AN: 41552

American (AMR) AF: 0.0427 AC: 654 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 224 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.101 AC: 485 AN: 4822

European-Finnish (FIN) AF: 0.0444 AC: 470 AN: 10586

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0951 AC: 6470 AN: 68014

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0743 Hom.: 185

Bravo AF: 0.0569

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.30
PhyloP100		0.10
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: rs10485821; hg19: chr20-1234390;