rs387035

Positions:

• chr20-1253599-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001384355.1(RAD21L1):​c.1480-670A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 152,178 control chromosomes in the GnomAD database, including 35 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 0.012 (35 hom., cov: 32)
• Consequence: RAD21L1 NM_001384355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1834/152178) while in subpopulation AFR AF= 0.0425 (1766/41534). AF 95% confidence interval is 0.0409. There are 35 homozygotes in gnomad4. There are 847 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1834 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD21L1	NM_001384355.1	c.1480-670A>G		intron_variant		ENST00000683101.1	NP_001371284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD21L1	ENST00000683101.1	c.1480-670A>G		intron_variant			NM_001384355.1	ENSP00000507397	A1
RAD21L1	ENST00000409241.5	c.1483-670A>G		intron_variant		1		ENSP00000386414	P4
RAD21L1	ENST00000402452.5	c.1386+4896A>G		intron_variant		5		ENSP00000385925

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1837 AN: 152060 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00717

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

GnomAD4 genome AF: 0.0121 AC: 1834 AN: 152178 Hom.: 35 Cov.: 32 AF XY: 0.0114 AC XY: 847 AN XY: 74388

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.0121 Hom.: 4

Bravo AF: 0.0139

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.42

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: rs387035; hg19: chr20-1234243;