rs139571703

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

Scores

2
4
12

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.10
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 -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
IGLL1NM_020070.4 linkuse as main transcriptc.475G>A p.Gly159Ser missense_variant 3/3 ENST00000330377.3 NP_064455.1 P15814-1
IGLL1NM_001369906.1 linkuse as main transcriptc.478G>A p.Gly160Ser missense_variant 3/3 NP_001356835.1
IGLL1NM_152855.3 linkuse as main transcriptc.*104G>A 3_prime_UTR_variant 2/2 NP_690594.1 P15814-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGLL1ENST00000330377.3 linkuse as main transcriptc.475G>A p.Gly159Ser missense_variant 3/31 NM_020070.4 ENSP00000329312.2 P15814-1
IGLL1ENST00000249053.3 linkuse as main transcriptc.*104G>A 3_prime_UTR_variant 2/21 ENSP00000249053.3 P15814-2
IGLL1ENST00000438703.1 linkuse as main transcriptc.478G>A p.Gly160Ser missense_variant 3/32 ENSP00000403391.1 C9JEE0
ENSG00000224277ENST00000458318.2 linkuse as main transcriptn.391-32C>T intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0309
AC:
4692
AN:
151930
Hom.:
80
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0258
Gnomad AMI
AF:
0.0296
Gnomad AMR
AF:
0.0217
Gnomad ASJ
AF:
0.0300
Gnomad EAS
AF:
0.0211
Gnomad SAS
AF:
0.0467
Gnomad FIN
AF:
0.0296
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.0359
Gnomad OTH
AF:
0.0321
GnomAD3 exomes
AF:
0.0331
AC:
8304
AN:
251212
Hom.:
153
AF XY:
0.0341
AC XY:
4635
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.0263
Gnomad AMR exome
AF:
0.0187
Gnomad ASJ exome
AF:
0.0323
Gnomad EAS exome
AF:
0.0226
Gnomad SAS exome
AF:
0.0450
Gnomad FIN exome
AF:
0.0344
Gnomad NFE exome
AF:
0.0366
Gnomad OTH exome
AF:
0.0352
GnomAD4 exome
AF:
0.0343
AC:
50105
AN:
1460896
Hom.:
870
Cov.:
33
AF XY:
0.0351
AC XY:
25485
AN XY:
726790
show subpopulations
Gnomad4 AFR exome
AF:
0.0244
Gnomad4 AMR exome
AF:
0.0196
Gnomad4 ASJ exome
AF:
0.0320
Gnomad4 EAS exome
AF:
0.0156
Gnomad4 SAS exome
AF:
0.0449
Gnomad4 FIN exome
AF:
0.0373
Gnomad4 NFE exome
AF:
0.0349
Gnomad4 OTH exome
AF:
0.0331
GnomAD4 genome
AF:
0.0309
AC:
4691
AN:
152048
Hom.:
81
Cov.:
32
AF XY:
0.0307
AC XY:
2281
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.0258
Gnomad4 AMR
AF:
0.0216
Gnomad4 ASJ
AF:
0.0300
Gnomad4 EAS
AF:
0.0209
Gnomad4 SAS
AF:
0.0465
Gnomad4 FIN
AF:
0.0296
Gnomad4 NFE
AF:
0.0359
Gnomad4 OTH
AF:
0.0313
Alfa
AF:
0.0355
Hom.:
34
Bravo
AF:
0.0295
TwinsUK
AF:
0.0291
AC:
108
ALSPAC
AF:
0.0314
AC:
121
ESP6500AA
AF:
0.0275
AC:
121
ESP6500EA
AF:
0.0379
AC:
326
ExAC
AF:
0.0338
AC:
4103
EpiCase
AF:
0.0363
EpiControl
AF:
0.0373

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Agammaglobulinemia 2, autosomal recessive Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.15
N
LIST_S2
Uncertain
0.93
D;D
MetaRNN
Benign
0.010
T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Benign
0.43
T
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.051
T;.
Polyphen
0.61
P;.
Vest4
0.12
MPC
0.27
ClinPred
0.037
T
GERP RS
2.5
Varity_R
0.76
gMVP
0.51

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

LitVar

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

Other links and lift over

dbSNP: rs139571703; hg19: chr22-23915620; COSMIC: COSV50770446; COSMIC: COSV50770446; API