rs3819309

Variant names:

• chr22-22327407-G-A
• rs3819309
• ENST00000390291.2:c.46+11G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

IGL (HGNC:5853):

ENSG00000286129 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGL		n.22327407G>A		intragenic_variant
IGLV1-50	unassigned_transcript_3574	c.46+11G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGLV1-50	ENST00000390291.2	c.46+11G>A		intron_variant	Intron 1 of 1	6		ENSP00000374826.2
ENSG00000286129	ENST00000652112.1	n.2667-1487G>A		intron_variant	Intron 13 of 13

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

GnomAD2 exomes AF: 0.242 AC: 58291 AN: 241200 AF XY: 0.239

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 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

African (AFR) AF: 0.163 AC: 2883 AN: 17678

American (AMR) AF: 0.346 AC: 15020 AN: 43438

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4337 AN: 20942

East Asian (EAS) AF: 0.164 AC: 5928 AN: 36060

South Asian (SAS) AF: 0.250 AC: 17472 AN: 69778

European-Finnish (FIN) AF: 0.289 AC: 15296 AN: 52968

Middle Eastern (MID) AF: 0.159 AC: 661 AN: 4146

European-Non Finnish (NFE) AF: 0.226 AC: 79147 AN: 349498

Other (OTH) AF: 0.216 AC: 7141 AN: 33046

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

African (AFR) AF: 0.168 AC: 6947 AN: 41470

American (AMR) AF: 0.275 AC: 4199 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3470

East Asian (EAS) AF: 0.147 AC: 753 AN: 5116

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4824

European-Finnish (FIN) AF: 0.279 AC: 2949 AN: 10584

Middle Eastern (MID) AF: 0.0828 AC: 24 AN: 290

European-Non Finnish (NFE) AF: 0.224 AC: 15224 AN: 67972

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.221 Hom.: 10180

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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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