chr22-23573314-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_020070.4(IGLL1):c.594C>T(p.His198His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,612,900 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

IGLL1
NM_020070.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.122

Publications

2 publications found

Variant links:

Genes affected

IGLL1 (HGNC:5870): (immunoglobulin lambda like polypeptide 1) The preB cell receptor is found on the surface of proB and preB cells, where it is involved in transduction of signals for cellular proliferation, differentiation from the proB cell to the preB cell stage, allelic exclusion at the Ig heavy chain gene locus, and promotion of Ig light chain gene rearrangements. The preB cell receptor is composed of a membrane-bound Ig mu heavy chain in association with a heterodimeric surrogate light chain. This gene encodes one of the surrogate light chain subunits and is a member of the immunoglobulin gene superfamily. This gene does not undergo rearrangement. Mutations in this gene can result in B cell deficiency and agammaglobulinemia, an autosomal recessive disease in which few or no gamma globulins or antibodies are made. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

IGLL1 Gene-Disease associations (from GenCC):

agammaglobulinemia 2, autosomal recessive
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
autosomal agammaglobulinemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IGLL1 links:

ENSG00000224277 (HGNC:):

ENSG00000224277 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 22-23573314-G-A is Benign according to our data. Variant chr22-23573314-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 712794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.122 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 Unknown,AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGLL1	NM_020070.4 link	c.594C>T	p.His198His	synonymous_variant	Exon 3 of 3	ENST00000330377.3	NP_064455.1	P15814-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGLL1	ENST00000330377.3 link	c.594C>T	p.His198His	synonymous_variant	Exon 3 of 3	1	NM_020070.4	ENSP00000329312.2		P15814-1

Frequencies

GnomAD3 genomes

AF:

0.000271

AC:

AN:

151432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000724

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000777

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000287

AC:

AN:

251250

AF XY:

0.000287

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1461348

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

182

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.000509

AC:

AN:

33376

American (AMR)

AF:

0.000784

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39692

South Asian (SAS)

AF:

0.000429

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.000210

AC:

233

AN:

1111736

Other (OTH)

AF:

0.000397

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000290

AC:

AN:

151552

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.000364

AC:

AN:

41164

American (AMR)

AF:

0.000723

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000779

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67904

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000695

Hom.:

7645

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IGLL1: BP4, BP7 -

Agammaglobulinemia 2, autosomal recessive

Benign:1

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.38

(source)

DANN

Benign

0.79

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism

(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

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chr22-23573314-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over