chr22-23573423-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020070.4(IGLL1):c.485T>C(p.Met162Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000755 in 1,613,832 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M162K) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 25 hom. )

Consequence

IGLL1
NM_020070.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.91

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

agammaglobulinemia 2, autosomal recessive
Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
autosomal agammaglobulinemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IGLL1 links:

ENSG00000224277 (HGNC:):

ENSG00000224277 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004740596).

BP6

Variant 22-23573423-A-G is Benign according to our data. Variant chr22-23573423-A-G is described in ClinVar as Benign. ClinVar VariationId is 779697.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 25 AR,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020070.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGLL1	NM_020070.4	MANE Select	c.485T>C	p.Met162Thr	missense	Exon 3 of 3	NP_064455.1	P15814-1
IGLL1	NM_001369906.1		c.488T>C	p.Met163Thr	missense	Exon 3 of 3	NP_001356835.1
IGLL1	NM_152855.3		c.*114T>C		3_prime_UTR	Exon 2 of 2	NP_690594.1	P15814-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGLL1	ENST00000330377.3	TSL:1 MANE Select	c.485T>C	p.Met162Thr	missense	Exon 3 of 3	ENSP00000329312.2	P15814-1
IGLL1	ENST00000249053.3	TSL:1	c.*114T>C		3_prime_UTR	Exon 2 of 2	ENSP00000249053.3	P15814-2
IGLL1	ENST00000438703.1	TSL:2	c.488T>C	p.Met163Thr	missense	Exon 3 of 3	ENSP00000403391.1	C9JEE0

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00156

AC:

392

AN:

251276

AF XY:

0.00205

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000776

AC:

1134

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

811

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0124

AC:

1072

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111804

Other (OTH)

AF:

0.000845

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

186

280

373

466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000558

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41532

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.0162

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00194

AC:

236

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Agammaglobulinemia 2, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.37

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.076

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.9

PhyloP100

1.9

PrimateAI

Benign

0.46

PROVEAN

Benign

2.1

REVEL

Benign

0.079

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.071

MVP

0.014

MPC

0.058

ClinPred

0.019

GERP RS

1.4

Varity_R

0.18

gMVP

0.26

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over