Genetic Variant ENST00000390291.2:c.46+11G>A (chr22-22327407-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.21

Publications

10 publications found

Variant links:

COSMIC-nc: COSV66506978

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 links:

IGL (HGNC:5853):

IGL links:

ENSG00000286129 (HGNC:):

ENSG00000286129 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.46+11G>A		intron_variant	Intron 1 of 1	6		ENSP00000374826.2		A0A075B6I6
ENSG00000286129	ENST00000652112.1 link	n.2667-1487G>A		intron_variant	Intron 13 of 13

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32540

AN:

151904

Hom.:

3642

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.234

AC XY:

80102

AN XY:

341940

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

7293

14586

21879

29172

36465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.214

AC:

32562

AN:

152018

Hom.:

3646

Cov.:

AF XY:

0.218

AC XY:

16216

AN XY:

74312

show subpopulations

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:

AN:

290

European-Non Finnish (NFE)

AF:

0.224

AC:

15224

AN:

67972

Other (OTH)

AF:

0.175

AC:

370

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1303

2606

3910

5213

6516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.53

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000390291.2:c.46+11G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over