rs2201845

Variant names:

• chr11-36534708-G-A
• rs2201845
• ENST00000534663.1:n.-470-1268G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-36534708-G-A
• chr11-36534708-G-T

Variant summary

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

The ENST00000534663.1(RAG1):​n.-470-1268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,984 control chromosomes in the GnomAD database, including 2,351 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 0.17 (2351 hom., cov: 32)
• Consequence: RAG1 ENST00000534663.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAG1	NM_001377277.1	c.-129+11264G>A		intron_variant	Intron 3 of 4		NP_001364206.1
RAG1	NM_001377278.1	c.-129+14479G>A		intron_variant	Intron 2 of 3		NP_001364207.1
RAG1	NM_001377279.1	c.-129+24171G>A		intron_variant	Intron 1 of 2		NP_001364208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAG1	ENST00000534663.1	n.-470-1268G>A		intron_variant	Intron 2 of 9	1		ENSP00000434610.1
RAG1	ENST00000697713.1	c.-131+24171G>A		intron_variant	Intron 1 of 2			ENSP00000513411.1
RAG1	ENST00000697714.1	c.-15+24171G>A		intron_variant	Intron 1 of 1			ENSP00000513412.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25055 AN: 151866 Hom.: 2339 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.165 AC: 25111 AN: 151984 Hom.: 2351 Cov.: 32 AF XY: 0.163 AC XY: 12112 AN XY: 74282

African (AFR) AF: 0.256 AC: 10594 AN: 41424

American (AMR) AF: 0.0991 AC: 1513 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 587 AN: 3462

East Asian (EAS) AF: 0.0465 AC: 241 AN: 5182

South Asian (SAS) AF: 0.152 AC: 734 AN: 4816

European-Finnish (FIN) AF: 0.152 AC: 1611 AN: 10564

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.139 AC: 9423 AN: 67950

Other (OTH) AF: 0.159 AC: 336 AN: 2112

Alfa AF: 0.107 Hom.: 219

Bravo AF: 0.163

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.63
PhyloP100		0.93

Splicing

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

Other links and lift over

dbSNP: rs2201845; hg19: chr11-36556258;