GeneBe

rs115303391

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020070.4(IGLL1):​c.300C>T​(p.Ser100Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00673 in 1,613,186 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 284 hom., cov: 32)
Exomes 𝑓: 0.0039 ( 247 hom. )

Consequence

IGLL1
NM_020070.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.34
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 22-23574989-G-A is Benign according to our data. Variant chr22-23574989-G-A is described in ClinVar as [Benign]. Clinvar id is 471477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.34 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGLL1NM_020070.4 linkuse as main transcriptc.300C>T p.Ser100Ser synonymous_variant 2/3 ENST00000330377.3 NP_064455.1 P15814-1
IGLL1NM_001369906.1 linkuse as main transcriptc.303C>T p.Ser101Ser synonymous_variant 2/3 NP_001356835.1
IGLL1NM_152855.3 linkuse as main transcriptc.207-1404C>T intron_variant NP_690594.1 P15814-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGLL1ENST00000330377.3 linkuse as main transcriptc.300C>T p.Ser100Ser synonymous_variant 2/31 NM_020070.4 ENSP00000329312.2 P15814-1
IGLL1ENST00000249053.3 linkuse as main transcriptc.207-1404C>T intron_variant 1 ENSP00000249053.3 P15814-2
IGLL1ENST00000438703.1 linkuse as main transcriptc.303C>T p.Ser101Ser synonymous_variant 2/32 ENSP00000403391.1 C9JEE0

Frequencies

GnomAD3 genomes
AF:
0.0341
AC:
5194
AN:
152096
Hom.:
284
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0123
Gnomad ASJ
AF:
0.00808
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000618
Gnomad OTH
AF:
0.0224
GnomAD3 exomes
AF:
0.00950
AC:
2388
AN:
251442
Hom.:
140
AF XY:
0.00707
AC XY:
961
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.122
Gnomad AMR exome
AF:
0.00561
Gnomad ASJ exome
AF:
0.00982
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000721
Gnomad OTH exome
AF:
0.00505
GnomAD4 exome
AF:
0.00387
AC:
5652
AN:
1460972
Hom.:
247
Cov.:
31
AF XY:
0.00334
AC XY:
2429
AN XY:
726856
show subpopulations
Gnomad4 AFR exome
AF:
0.120
Gnomad4 AMR exome
AF:
0.00675
Gnomad4 ASJ exome
AF:
0.00949
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000516
Gnomad4 OTH exome
AF:
0.00822
GnomAD4 genome
AF:
0.0342
AC:
5201
AN:
152214
Hom.:
284
Cov.:
32
AF XY:
0.0330
AC XY:
2459
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.118
Gnomad4 AMR
AF:
0.0123
Gnomad4 ASJ
AF:
0.00808
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000618
Gnomad4 OTH
AF:
0.0222
Alfa
AF:
0.0145
Hom.:
46
Bravo
AF:
0.0388
Asia WGS
AF:
0.00549
AC:
19
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.00119

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Agammaglobulinemia 2, autosomal recessive Benign:2
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesSep 21, 2023- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.1
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115303391; hg19: chr22-23917176; API