chr20-1247449-G-A

Variant names:

• chr20-1247449-G-A
• rs1923876
• NM_001384355.1:c.1401+1144G>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.1401+1144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 152,176 control chromosomes in the GnomAD database, including 475 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 0.067 (475 hom., cov: 32)
• Consequence: RAD21L1 NM_001384355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21L1	NM_001384355.1	MANE Select	c.1401+1144G>A		intron	N/A	NP_001371284.1	A0A804HJ87
	RAD21L1	NM_001136566.3		c.1404+1144G>A		intron	N/A	NP_001130038.2	Q9H4I0-1
	RAD21L1	NM_001384356.1		c.927+1144G>A		intron	N/A	NP_001371285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21L1	ENST00000683101.1	MANE Select	c.1401+1144G>A		intron	N/A	ENSP00000507397.1	A0A804HJ87
	RAD21L1	ENST00000409241.5	TSL:1	c.1404+1144G>A		intron	N/A	ENSP00000386414.1	Q9H4I0-1
	RAD21L1	ENST00000402452.5	TSL:5	c.1309-1177G>A		intron	N/A	ENSP00000385925.1	Q9H4I0-2

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10203 AN: 152058 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0670 AC: 10197 AN: 152176 Hom.: 475 Cov.: 32 AF XY: 0.0668 AC XY: 4972 AN XY: 74412

African (AFR) AF: 0.0164 AC: 681 AN: 41528

American (AMR) AF: 0.0616 AC: 941 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 133 AN: 3462

East Asian (EAS) AF: 0.175 AC: 905 AN: 5176

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4822

European-Finnish (FIN) AF: 0.107 AC: 1134 AN: 10584

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0890 AC: 6052 AN: 68006

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0659 Hom.: 138

Bravo AF: 0.0638

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.47
PhyloP100		0.027
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: rs1923876; hg19: chr20-1228093;