rs75088277

Positions:

• chr22-23573359-G-A
• chr22-23573359-G-C
• chr22-23573359-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020070.4(IGLL1):​c.549C>T​(p.Pro183Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,614,050 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (113 hom., cov: 32)
  • Exomes 𝑓: 0.013 (236 hom.)
• Consequence: IGLL1 NM_020070.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.959

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]

ENSG00000224277 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 22-23573359-G-A is Benign according to our data. Variant chr22-23573359-G-A is described in ClinVar as [Benign]. Clinvar id is 478775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23573359-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.959 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGLL1	NM_020070.4	c.549C>T	p.Pro183Pro	synonymous_variant	3/3	ENST00000330377.3	NP_064455.1
IGLL1	NM_001369906.1	c.552C>T	p.Pro184Pro	synonymous_variant	3/3		NP_001356835.1
IGLL1	NM_152855.3	c.*178C>T		3_prime_UTR_variant	2/2		NP_690594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGLL1	ENST00000330377.3	c.549C>T	p.Pro183Pro	synonymous_variant	3/3	1	NM_020070.4	ENSP00000329312.2
IGLL1	ENST00000249053.3	c.*178C>T		3_prime_UTR_variant	2/2	1		ENSP00000249053.3
ENSG00000224277	ENST00000458318.2	n.391-106G>A		intron_variant		3
IGLL1	ENST00000438703.1	c.*10C>T		downstream_gene_variant		2		ENSP00000403391.1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4109 AN: 152080 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.0126

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.0144 AC: 3614 AN: 251424 Hom.: 76 AF XY: 0.0132 AC XY: 1795 AN XY: 135898

Gnomad AFR exome AF: 0.0736

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.0100

Gnomad SAS exome AF: 0.0142

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.0129 AC: 18887 AN: 1461852 Hom.: 236 Cov.: 32 AF XY: 0.0125 AC XY: 9098 AN XY: 727228

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.0149

Gnomad4 ASJ exome AF: 0.00256

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.00170

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0271 AC: 4121 AN: 152198 Hom.: 113 Cov.: 32 AF XY: 0.0256 AC XY: 1903 AN XY: 74400

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.0200

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0136 Hom.: 14

Bravo AF: 0.0304

Asia WGS AF: 0.0290 AC: 101 AN: 3478

EpiCase AF: 0.00932

EpiControl AF: 0.00919

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Agammaglobulinemia 2, autosomal recessive Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs75088277; hg19: chr22-23915546; COSMIC: COSV50770264; COSMIC: COSV50770264;