rs2201845

Positions:

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

Variant summary

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

The NM_001377277.1(RAG1):​c.-129+11264G>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 NM_001377277.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RAG1	NM_001377277.1	c.-129+11264G>A		intron_variant			NP_001364206.1
RAG1	NM_001377278.1	c.-129+14479G>A		intron_variant			NP_001364207.1
RAG1	NM_001377279.1	c.-129+24171G>A		intron_variant			NP_001364208.1
RAG1	NM_001377280.1	c.-15+24171G>A		intron_variant			NP_001364209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAG1	ENST00000534663.1	n.-470-1268G>A		intron_variant		1		ENSP00000434610.1
RAG1	ENST00000697713.1	c.-131+24171G>A		intron_variant				ENSP00000513411.1
RAG1	ENST00000697714.1	c.-15+24171G>A		intron_variant				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

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.0991

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0465

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.159

Alfa AF: 0.103 Hom.: 195

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2201845; hg19: chr11-36556258;