11-36511020-C-T

Position:

• chr11-36511020-C-T

Variant summary

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

The NM_001377277.1(RAG1):​c.-289+483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 152,232 control chromosomes in the GnomAD database, including 68,958 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 0.95 (68951 hom., cov: 32)
  • Exomes 𝑓: 1.0 (7 hom.)
• Consequence: RAG1 NM_001377277.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

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 (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAG1	NM_001377277.1	c.-289+483C>T		intron_variant			NP_001364206.1
RAG1	NM_001377278.1	c.-227+483C>T		intron_variant			NP_001364207.1
RAG1	NM_001377279.1	c.-129+483C>T		intron_variant			NP_001364208.1
RAG1	NM_001377280.1	c.-15+483C>T		intron_variant			NP_001364209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAG1	ENST00000697713.1	c.-131+483C>T		intron_variant				ENSP00000513411	P1
RAG1	ENST00000697714.1	c.-15+483C>T		intron_variant				ENSP00000513412	P1
RAG1	ENST00000697715.1	c.-289+483C>T		intron_variant				ENSP00000513413	P1
RAG1	ENST00000529126.5	n.312C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144276 AN: 152100 Hom.: 68904 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.976

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.963

GnomAD4 exome AF: 1.00 AC: 14 AN: 14 Hom.: 7 Cov.: 0 AF XY: 1.00 AC XY: 12 AN XY: 12

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.949 AC: 144381 AN: 152218 Hom.: 68951 Cov.: 32 AF XY: 0.950 AC XY: 70740 AN XY: 74428

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 0.993

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.977

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.963

Alfa AF: 0.987 Hom.: 62935

Bravo AF: 0.943

Asia WGS AF: 0.971 AC: 3377 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	4.0
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs331449; hg19: chr11-36532570;