rs8138122

Positions:

chr22-23573342-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020070.4(IGLL1):c.566G>A(p.Arg189His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00715 in 1,613,992 control chromosomes in the GnomAD database, including 464 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.032 ( 217 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 247 hom. )

Consequence

IGLL1
NM_020070.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.220

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024659336).

BP6

Variant 22-23573342-C-T is Benign according to our data. Variant chr22-23573342-C-T is described in ClinVar as [Benign]. Clinvar id is 487215.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23573342-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IGLL1	NM_020070.4 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	3/3	ENST00000330377.3
IGLL1	NM_001369906.1 linkuse as main transcript	c.569G>A	p.Arg190His	missense_variant	3/3
IGLL1	NM_152855.3 linkuse as main transcript	c.*195G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGLL1	ENST00000330377.3 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	3/3	1	NM_020070.4	P1	P15814-1
IGLL1	ENST00000249053.3 linkuse as main transcript	c.*195G>A		3_prime_UTR_variant	2/2	1			P15814-2
	ENST00000458318.2 linkuse as main transcript	n.391-123C>T		intron_variant, non_coding_transcript_variant		3
IGLL1	ENST00000438703.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4903

AN:

152012

Hom.:

218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.0315

GnomAD3 exomes

AF:

0.00983

AC:

2472

AN:

251436

Hom.:

AF XY:

0.00786

AC XY:

1068

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.00934

Gnomad ASJ exome

AF:

0.00953

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.00961

GnomAD4 exome

AF:

0.00453

AC:

6617

AN:

1461862

Hom.:

247

Cov.:

AF XY:

0.00417

AC XY:

3031

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.00999

Gnomad4 ASJ exome

AF:

0.00872

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.0323

AC:

4917

AN:

152130

Hom.:

217

Cov.:

AF XY:

0.0320

AC XY:

2379

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0168

Hom.:

Bravo

AF:

0.0369

ESP6500AA

AF:

0.106

AC:

466

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.0116

AC:

1410

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00290

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Agammaglobulinemia 2, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.81

DANN

Benign

0.70

DEOGEN2

Benign

0.068

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00048

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.65

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

3.6

REVEL

Benign

0.0090

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.024

MPC

0.062

ClinPred

0.0026

GERP RS

-4.3

Varity_R

0.085

gMVP

0.29

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