chr22-22327407-G-A

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390291.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGLV1-50	ENST00000390291.2	TSL:6	c.46+11G>A		intron	N/A	ENSP00000374826.2	A0A075B6I6
	ENSG00000286129	ENST00000652112.1		n.2667-1487G>A		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3819309;

hg19: chr22-22681765;

COSMIC: COSV66506978;