11-36510938-T-G

Variant names:

• chr11-36510938-T-G
• rs5030416
• ENST00000529126.5:n.230T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000529126.5(RAG1):​n.230T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,216 control chromosomes in the GnomAD database, including 1,609 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 0.14 (1609 hom., cov: 32)
  • Exomes 𝑓: 0.18 (0 hom.)
• Consequence: RAG1 ENST00000529126.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 12 publications found

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]

RAG1 Gene-Disease associations (from GenCC):

• immunodeficiency disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• Omenn syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Genomics England PanelApp, Ambry Genetics
• recombinase activating gene 1 deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• combined immunodeficiency due to partial RAG1 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529126.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAG1	NM_001440489.1		c.-115T>G		5_prime_UTR	Exon 1 of 2	NP_001427418.1
	RAG1	NM_001377277.1		c.-289+401T>G		intron	N/A	NP_001364206.1
	RAG1	NM_001377278.1		c.-227+401T>G		intron	N/A	NP_001364207.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAG1	ENST00000529126.5	TSL:3	n.230T>G		non_coding_transcript_exon	Exon 1 of 3
	RAG1	ENST00000697713.1		c.-131+401T>G		intron	N/A	ENSP00000513411.1
	RAG1	ENST00000697714.1		c.-15+401T>G		intron	N/A	ENSP00000513412.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21703 AN: 152076 Hom.: 1609 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.182 AC: 4 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 3 AN: 18

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.143 AC: 21715 AN: 152194 Hom.: 1609 Cov.: 32 AF XY: 0.143 AC XY: 10668 AN XY: 74408

African (AFR) AF: 0.152 AC: 6319 AN: 41528

American (AMR) AF: 0.199 AC: 3034 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3472

East Asian (EAS) AF: 0.148 AC: 766 AN: 5172

South Asian (SAS) AF: 0.0779 AC: 376 AN: 4828

European-Finnish (FIN) AF: 0.136 AC: 1445 AN: 10600

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9040 AN: 67990

Other (OTH) AF: 0.136 AC: 288 AN: 2116

Alfa AF: 0.128 Hom.: 2811

Bravo AF: 0.150

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.69
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs5030416; hg19: chr11-36532488;