rs74519217

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020070.4(IGLL1):c.507C>T(p.Ser169Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,614,034 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 73 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 86 hom. )

Consequence

IGLL1
NM_020070.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00300

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 22-23573401-G-A is Benign according to our data. Variant chr22-23573401-G-A is described in ClinVar as [Benign]. Clinvar id is 471478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGLL1	NM_020070.4 link	c.507C>T	p.Ser169Ser	synonymous_variant	Exon 3 of 3	ENST00000330377.3	NP_064455.1	P15814-1
IGLL1	NM_001369906.1 link	c.510C>T	p.Ser170Ser	synonymous_variant	Exon 3 of 3		NP_001356835.1
IGLL1	NM_152855.3 link	c.*136C>T		3_prime_UTR_variant	Exon 2 of 2		NP_690594.1	P15814-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGLL1	ENST00000330377.3 link	c.507C>T	p.Ser169Ser	synonymous_variant	Exon 3 of 3	1	NM_020070.4	ENSP00000329312.2	P15814-1
IGLL1	ENST00000249053 link	c.*136C>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000249053.3	P15814-2
IGLL1	ENST00000438703.1 link	c.510C>T	p.Ser170Ser	synonymous_variant	Exon 3 of 3	2		ENSP00000403391.1	C9JEE0
ENSG00000224277	ENST00000458318.2 link	n.391-64G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2863

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00509

AC:

1279

AN:

251448

Hom.:

AF XY:

0.00364

AC XY:

494

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0688

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00210

AC:

3064

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1307

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0752

Gnomad4 AMR exome

AF:

0.00429

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.00417

GnomAD4 genome

AF:

0.0188

AC:

2867

AN:

152248

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1345

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0652

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00624

Hom.:

Bravo

AF:

0.0216

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Agammaglobulinemia 2, autosomal recessive

Benign:2

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.2

DANN

Benign

0.64

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