rs139571703

Positions:

chr22-23573433-C-T

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

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]

IGLL1 links:

ENSG00000224277 (HGNC:):

ENSG00000224277 links:

Genome browser will be placed here

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 linkuse as main transcript	c.475G>A	p.Gly159Ser	missense_variant	3/3	ENST00000330377.3	NP_064455.1	P15814-1
IGLL1	NM_001369906.1 linkuse as main transcript	c.478G>A	p.Gly160Ser	missense_variant	3/3		NP_001356835.1
IGLL1	NM_152855.3 linkuse as main transcript	c.*104G>A		3_prime_UTR_variant	2/2		NP_690594.1	P15814-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGLL1	ENST00000330377.3 linkuse as main transcript	c.475G>A	p.Gly159Ser	missense_variant	3/3	1	NM_020070.4	ENSP00000329312.2	P15814-1
IGLL1	ENST00000249053.3 linkuse as main transcript	c.*104G>A		3_prime_UTR_variant	2/2	1		ENSP00000249053.3	P15814-2
IGLL1	ENST00000438703.1 linkuse as main transcript	c.478G>A	p.Gly160Ser	missense_variant	3/3	2		ENSP00000403391.1	C9JEE0
ENSG00000224277	ENST00000458318.2 linkuse as main transcript	n.391-32C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4692

AN:

151930

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

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 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.43

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over