rs3819309

Positions:

• chr22-22327407-G-A

Variant summary

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

The ENST00000390291.2(IGLV1-50):​c.46+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 779,572 control chromosomes in the GnomAD database, including 22,227 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 0.21 (3646 hom., cov: 32)
  • Exomes 𝑓: 0.24 (18581 hom.)
• Consequence: IGLV1-50 ENST00000390291.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

Genes affected

IGLV1-50 (HGNC:5881): (immunoglobulin lambda variable 1-50 (non-functional)) Predicted to be involved in immune response. Predicted to be located in plasma membrane. Predicted to be part of immunoglobulin complex. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IGLV1-50 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGLV1-50	unassigned_transcript_3575	c.46+11G>A		intron_variant
IGL		n.22327407G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGLV1-50	ENST00000390291.2	c.46+11G>A		intron_variant		6		ENSP00000374826.2
ENSG00000286129	ENST00000652112.1	n.2667-1487G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32540 AN: 151904 Hom.: 3642 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.0897

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.242 AC: 58291 AN: 241200 Hom.: 7584 AF XY: 0.239 AC XY: 31468 AN XY: 131880

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.249

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.236 AC: 147885 AN: 627554 Hom.: 18581 Cov.: 0 AF XY: 0.234 AC XY: 80102 AN XY: 341940

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.214 AC: 32562 AN: 152018 Hom.: 3646 Cov.: 32 AF XY: 0.218 AC XY: 16216 AN XY: 74312

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.175

Alfa AF: 0.222 Hom.: 6928

Asia WGS AF: 0.186 AC: 647 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3819309; hg19: chr22-22681765; COSMIC: COSV66506978;