22-23573423-A-T

Position:

chr22-23573423-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020070.4(IGLL1):c.485T>A(p.Met162Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,613,580 control chromosomes in the GnomAD database, including 771 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M162T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.039 ( 152 hom., cov: 32)

Exomes 𝑓: 0.026 ( 619 hom. )

Consequence

IGLL1
NM_020070.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.91

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031225085).

BP6

Variant 22-23573423-A-T is Benign according to our data. Variant chr22-23573423-A-T is described in ClinVar as [Benign]. Clinvar id is 439820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23573423-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IGLL1	NM_020070.4 linkuse as main transcript	c.485T>A	p.Met162Lys	missense_variant	3/3	ENST00000330377.3
IGLL1	NM_001369906.1 linkuse as main transcript	c.488T>A	p.Met163Lys	missense_variant	3/3
IGLL1	NM_152855.3 linkuse as main transcript	c.*114T>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.485T>A	p.Met162Lys	missense_variant	3/3	1	NM_020070.4	P1	P15814-1
IGLL1	ENST00000249053.3 linkuse as main transcript	c.*114T>A		3_prime_UTR_variant	2/2	1			P15814-2
	ENST00000458318.2 linkuse as main transcript	n.391-42A>T		intron_variant, non_coding_transcript_variant		3
IGLL1	ENST00000438703.1 linkuse as main transcript	c.488T>A	p.Met163Lys	missense_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5980

AN:

152058

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0663

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0818

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0393

GnomAD3 exomes

AF:

0.0305

AC:

7661

AN:

251276

Hom.:

150

AF XY:

0.0302

AC XY:

4100

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0638

Gnomad AMR exome

AF:

0.0168

Gnomad ASJ exome

AF:

0.0860

Gnomad EAS exome

AF:

0.0118

Gnomad SAS exome

AF:

0.0173

Gnomad FIN exome

AF:

0.0467

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0351

GnomAD4 exome

AF:

0.0260

AC:

37979

AN:

1461406

Hom.:

619

Cov.:

AF XY:

0.0260

AC XY:

18898

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.0652

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.0900

Gnomad4 EAS exome

AF:

0.0111

Gnomad4 SAS exome

AF:

0.0191

Gnomad4 FIN exome

AF:

0.0451

Gnomad4 NFE exome

AF:

0.0232

Gnomad4 OTH exome

AF:

0.0333

GnomAD4 genome

AF:

0.0393

AC:

5985

AN:

152174

Hom.:

152

Cov.:

AF XY:

0.0393

AC XY:

2920

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0663

Gnomad4 AMR

AF:

0.0241

Gnomad4 ASJ

AF:

0.0818

Gnomad4 EAS

AF:

0.0117

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0389

Alfa

AF:

0.0274

Hom.:

Bravo

AF:

0.0396

TwinsUK

AF:

0.0256

AC:

ALSPAC

AF:

0.0171

AC:

ESP6500AA

AF:

0.0654

AC:

288

ESP6500EA

AF:

0.0293

AC:

252

ExAC

AF:

0.0312

AC:

3789

EpiCase

AF:

0.0277

EpiControl

AF:

0.0345

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Agammaglobulinemia 2, autosomal recessive

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.42

N;.

MutationTaster

Benign

0.99

D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.078

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0050

D;.

Polyphen

0.0010

B;.

Vest4

0.062

MPC

0.075

ClinPred

0.032

GERP RS

1.4

Varity_R

0.69

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