rs115303391

chr22-23574989-G-Achr22-23574989-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.300C>T(p.Ser100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00673 in 1,613,186 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (284 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (247 hom.)
• Consequence: IGLL1 NM_020070.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.34

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-23574989-G-A is Benign according to our data. Variant chr22-23574989-G-A is described in ClinVar as [Benign]. Clinvar id is 471477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGLL1	NM_020070.4	c.300C>T	p.Ser100=	synonymous_variant	2/3	ENST00000330377.3
IGLL1	NM_001369906.1	c.303C>T	p.Ser101=	synonymous_variant	2/3
IGLL1	NM_152855.3	c.207-1404C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGLL1	ENST00000330377.3	c.300C>T	p.Ser100=	synonymous_variant	2/3	1	NM_020070.4	P1
IGLL1	ENST00000249053.3	c.207-1404C>T		intron_variant		1
IGLL1	ENST00000438703.1	c.303C>T	p.Ser101=	synonymous_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5194 AN: 152096 Hom.: 284 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.0224

GnomAD3 exomes AF: 0.00950 AC: 2388 AN: 251442 Hom.: 140 AF XY: 0.00707 AC XY: 961 AN XY: 135896

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.00561

Gnomad ASJ exome AF: 0.00982

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000721

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00387 AC: 5652 AN: 1460972 Hom.: 247 Cov.: 31 AF XY: 0.00334 AC XY: 2429 AN XY: 726856

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.00675

Gnomad4 ASJ exome AF: 0.00949

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000516

Gnomad4 OTH exome AF: 0.00822

GnomAD4 genome AF: 0.0342 AC: 5201 AN: 152214 Hom.: 284 Cov.: 32 AF XY: 0.0330 AC XY: 2459 AN XY: 74418

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.00808

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0145 Hom.: 46

Bravo AF: 0.0388

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Agammaglobulinemia 2, autosomal recessive Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs115303391; hg19: chr22-23917176;