11-36510938-T-G

Variant names:

• chr11-36510938-T-G
• rs5030416
• NM_001377277.1:c.-289+401T>G

Variant summary

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

The NM_001377277.1(RAG1):​c.-289+401T>G variant causes a intron 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 NM_001377277.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAG1	NM_001377277.1	c.-289+401T>G		intron_variant	Intron 1 of 4		NP_001364206.1
RAG1	NM_001377278.1	c.-227+401T>G		intron_variant	Intron 1 of 3		NP_001364207.1
RAG1	NM_001377279.1	c.-129+401T>G		intron_variant	Intron 1 of 2		NP_001364208.1
RAG1	NM_001377280.1	c.-15+401T>G		intron_variant	Intron 1 of 1		NP_001364209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAG1	ENST00000697713.1	c.-131+401T>G		intron_variant	Intron 1 of 2			ENSP00000513411.1
RAG1	ENST00000697714.1	c.-15+401T>G		intron_variant	Intron 1 of 1			ENSP00000513412.1
RAG1	ENST00000697715.1	c.-289+401T>G		intron_variant	Intron 1 of 4			ENSP00000513413.1
RAG1	ENST00000529126.5	n.230T>G		non_coding_transcript_exon_variant	Exon 1 of 3	3

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

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.167

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

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.136

Alfa AF: 0.111 Hom.: 434

Bravo AF: 0.150

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5030416; hg19: chr11-36532488;