rs116275804

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020070.4(IGLL1):c.276C>T(p.Asn92Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,610,684 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 97 hom., cov: 32)

Exomes 𝑓: 0.013 ( 213 hom. )

Consequence

IGLL1
NM_020070.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.24

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 22-23575013-G-A is Benign according to our data. Variant chr22-23575013-G-A is described in ClinVar as Benign. ClinVar VariationId is 471475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGLL1	NM_020070.4 link	c.276C>T	p.Asn92Asn	synonymous_variant	Exon 2 of 3	ENST00000330377.3	NP_064455.1	P15814-1
IGLL1	NM_001369906.1 link	c.279C>T	p.Asn93Asn	synonymous_variant	Exon 2 of 3		NP_001356835.1
IGLL1	NM_152855.3 link	c.207-1428C>T		intron_variant	Intron 1 of 1		NP_690594.1	P15814-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGLL1	ENST00000330377.3 link	c.276C>T	p.Asn92Asn	synonymous_variant	Exon 2 of 3	1	NM_020070.4	ENSP00000329312.2	P15814-1
IGLL1	ENST00000249053.3 link	c.207-1428C>T		intron_variant	Intron 1 of 1	1		ENSP00000249053.3	P15814-2
IGLL1	ENST00000438703.1 link	c.279C>T	p.Asn93Asn	synonymous_variant	Exon 2 of 3	2		ENSP00000403391.1	C9JEE0

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3781

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.0125

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0150

AC:

3762

AN:

251372

AF XY:

0.0141

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.0182

GnomAD4 exome

AF:

0.0126

AC:

18399

AN:

1458414

Hom.:

213

Cov.:

AF XY:

0.0124

AC XY:

8974

AN XY:

725676

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0595

AC:

1978

AN:

33242

American (AMR)

AF:

0.0189

AC:

844

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0105

AC:

273

AN:

26122

East Asian (EAS)

AF:

0.0148

AC:

589

AN:

39688

South Asian (SAS)

AF:

0.0134

AC:

1152

AN:

86188

European-Finnish (FIN)

AF:

0.00161

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00903

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0113

AC:

12492

AN:

1109034

Other (OTH)

AF:

0.0155

AC:

933

AN:

60254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.370

Heterozygous variant carriers

678

1356

2033

2711

3389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

528

1056

1584

2112

2640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0249

AC:

3792

AN:

152270

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1726

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0587

AC:

2440

AN:

41536

American (AMR)

AF:

0.0209

AC:

320

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00835

AC:

AN:

3472

East Asian (EAS)

AF:

0.0126

AC:

AN:

5174

South Asian (SAS)

AF:

0.0141

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

771

AN:

68020

Other (OTH)

AF:

0.0274

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

185

371

556

742

927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0288

EpiCase

AF:

0.0104

EpiControl

AF:

0.00990

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Agammaglobulinemia 2, autosomal recessive

Benign:2

Nov 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.95

CADD

Benign

0.55

(source)

DANN

Benign

0.80

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

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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