rs139571703
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_020070.4(IGLL1):c.475G>A(p.Gly159Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,612,944 control chromosomes in the GnomAD database, including 951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 81 hom., cov: 32)
Exomes 𝑓: 0.034 ( 870 hom. )
Consequence
IGLL1
NM_020070.4 missense
NM_020070.4 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 3.10
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.010354221).
BP6
Variant 22-23573433-C-T is Benign according to our data. Variant chr22-23573433-C-T is described in ClinVar as [Benign]. Clinvar id is 478784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23573433-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0309 (4691/152048) while in subpopulation SAS AF= 0.0465 (224/4818). AF 95% confidence interval is 0.0415. There are 81 homozygotes in gnomad4. There are 2281 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 81 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IGLL1 | NM_020070.4 | c.475G>A | p.Gly159Ser | missense_variant | 3/3 | ENST00000330377.3 | NP_064455.1 | |
IGLL1 | NM_001369906.1 | c.478G>A | p.Gly160Ser | missense_variant | 3/3 | NP_001356835.1 | ||
IGLL1 | NM_152855.3 | c.*104G>A | 3_prime_UTR_variant | 2/2 | NP_690594.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IGLL1 | ENST00000330377.3 | c.475G>A | p.Gly159Ser | missense_variant | 3/3 | 1 | NM_020070.4 | ENSP00000329312.2 | ||
IGLL1 | ENST00000249053.3 | c.*104G>A | 3_prime_UTR_variant | 2/2 | 1 | ENSP00000249053.3 | ||||
IGLL1 | ENST00000438703.1 | c.478G>A | p.Gly160Ser | missense_variant | 3/3 | 2 | ENSP00000403391.1 | |||
ENSG00000224277 | ENST00000458318.2 | n.391-32C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0309 AC: 4692AN: 151930Hom.: 80 Cov.: 32
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GnomAD3 exomes AF: 0.0331 AC: 8304AN: 251212Hom.: 153 AF XY: 0.0341 AC XY: 4635AN XY: 135756
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GnomAD4 exome AF: 0.0343 AC: 50105AN: 1460896Hom.: 870 Cov.: 33 AF XY: 0.0351 AC XY: 25485AN XY: 726790
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GnomAD4 genome AF: 0.0309 AC: 4691AN: 152048Hom.: 81 Cov.: 32 AF XY: 0.0307 AC XY: 2281AN XY: 74322
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Agammaglobulinemia 2, autosomal recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
T;.
Polyphen
P;.
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at