rs5030490

chr11-36512635-T-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+2098T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 152,310 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 0.013 (35 hom., cov: 33)
• Consequence: RAG1 NM_001377277.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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 = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAG1	NM_001377277.1	c.-289+2098T>C		intron_variant
RAG1	NM_001377278.1	c.-227+2098T>C		intron_variant
RAG1	NM_001377279.1	c.-129+2098T>C		intron_variant
RAG1	NM_001377280.1	c.-15+2098T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAG1	ENST00000697713.1	c.-131+2098T>C		intron_variant				P1
RAG1	ENST00000697714.1	c.-15+2098T>C		intron_variant				P1
RAG1	ENST00000697715.1	c.-289+2098T>C		intron_variant				P1
RAG1	ENST00000529126.5	n.330+1597T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2044 AN: 152192 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.00331

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0762

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0119

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

GnomAD4 genome AF: 0.0134 AC: 2044 AN: 152310 Hom.: 35 Cov.: 33 AF XY: 0.0131 AC XY: 977 AN XY: 74466

Gnomad4 AFR AF: 0.00330

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.0761

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0142 Hom.: 4

Bravo AF: 0.0154

Asia WGS AF: 0.0330 AC: 115 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	5.3
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5030490; hg19: chr11-36534185;