rs5030411

chr11-36512203-G-Achr11-36512203-G-C

Variant summary

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

The NM_001377277.1(RAG1):c.-289+1666G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,032 control chromosomes in the GnomAD database, including 21,497 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 0.50 (21497 hom., cov: 32)
• Consequence: RAG1 NM_001377277.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

Genes affected

RAG1 (HGNC:9831): (recombination activating 1) The protein encoded by this gene is involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. Defects in this gene can be the cause of several diseases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAG1	NM_001377277.1	c.-289+1666G>A		intron_variant
RAG1	NM_001377278.1	c.-227+1666G>A		intron_variant
RAG1	NM_001377279.1	c.-129+1666G>A		intron_variant
RAG1	NM_001377280.1	c.-15+1666G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAG1	ENST00000697713.1	c.-131+1666G>A		intron_variant				P1
RAG1	ENST00000697714.1	c.-15+1666G>A		intron_variant				P1
RAG1	ENST00000697715.1	c.-289+1666G>A		intron_variant				P1
RAG1	ENST00000529126.5	n.330+1165G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75276 AN: 151914 Hom.: 21496 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.495 AC: 75281 AN: 152032 Hom.: 21497 Cov.: 32 AF XY: 0.501 AC XY: 37219 AN XY: 74316

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.517

Alfa AF: 0.589 Hom.: 44774

Bravo AF: 0.478

Asia WGS AF: 0.622 AC: 2166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.3
Dann	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5030411; hg19: chr11-36533753;