ENST00000249053.3:c.220C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000249053.3(IGLL1):c.220C>T(p.His74Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,226 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H74Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

IGLL1
ENST00000249053.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009215236).

BP6

Variant 22-23573572-G-A is Benign according to our data. Variant chr22-23573572-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 538833.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23573572-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGLL1	NM_020070.4 link	c.336C>T	p.Ala112Ala	synonymous_variant	Exon 3 of 3	ENST00000330377.3	NP_064455.1	P15814-1
IGLL1	NM_152855.3 link	c.220C>T	p.His74Tyr	missense_variant	Exon 2 of 2		NP_690594.1	P15814-2
IGLL1	NM_001369906.1 link	c.339C>T	p.Ala113Ala	synonymous_variant	Exon 3 of 3		NP_001356835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGLL1	ENST00000249053.3 link	c.220C>T	p.His74Tyr	missense_variant	Exon 2 of 2	1		ENSP00000249053.3	P15814-2
IGLL1	ENST00000330377.3 link	c.336C>T	p.Ala112Ala	synonymous_variant	Exon 3 of 3	1	NM_020070.4	ENSP00000329312.2	P15814-1
IGLL1	ENST00000438703.1 link	c.339C>T	p.Ala113Ala	synonymous_variant	Exon 3 of 3	2		ENSP00000403391.1	C9JEE0
ENSG00000224277	ENST00000458318.2 link	n.*65G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

172

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000558

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000805

AC:

202

AN:

251056

Hom.:

AF XY:

0.000766

AC XY:

104

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00136

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.000944

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00136

AC:

1990

AN:

1461208

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

962

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152018

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000557

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00271

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00113

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000873

AC:

106

EpiCase

AF:

0.00213

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Agammaglobulinemia 2, autosomal recessive

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.3

DANN

Benign

0.49

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.26

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0092

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.67

REVEL

Benign

0.010

Sift

Benign

0.17

Sift4G

Benign

0.46

Vest4

0.13

MVP

0.14

ClinPred

0.0026

GERP RS

-4.9

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