22-23573183-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020070.4(IGLL1):c.*83C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 1,310,578 control chromosomes in the GnomAD database, including 4,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1734 hom., cov: 32)
  • Exomes 𝑓: 0.048 (2374 hom.)
• Consequence: IGLL1 NM_020070.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.867

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-23573183-G-A is Benign according to our data. Variant chr22-23573183-G-A is described in ClinVar as [Benign]. Clinvar id is 1273962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGLL1	NM_020070.4	c.*83C>T		3_prime_UTR_variant	3/3	ENST00000330377.3
IGLL1	NM_001369906.1	c.*83C>T		3_prime_UTR_variant	3/3
IGLL1	NM_152855.3	c.*354C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGLL1	ENST00000330377.3	c.*83C>T		3_prime_UTR_variant	3/3	1	NM_020070.4	P1
IGLL1	ENST00000249053.3	c.*354C>T		3_prime_UTR_variant	2/2	1
	ENST00000458318.2	n.391-282G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16737 AN: 152052 Hom.: 1727 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0537

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0476 AC: 55151 AN: 1158408 Hom.: 2374 Cov.: 16 AF XY: 0.0477 AC XY: 28149 AN XY: 590446

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.0403

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.00998

Gnomad4 SAS exome AF: 0.0541

Gnomad4 FIN exome AF: 0.0505

Gnomad4 NFE exome AF: 0.0378

Gnomad4 OTH exome AF: 0.0655

GnomAD4 genome AF: 0.110 AC: 16777 AN: 152170 Hom.: 1734 Cov.: 32 AF XY: 0.108 AC XY: 8055 AN XY: 74414

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.0550

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.101

Alfa AF: 0.108 Hom.: 233

Bravo AF: 0.118

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.5
Dann	Benign	0.49

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: rs8141940; hg19: chr22-23915370; COSMIC: COSV50770124; COSMIC: COSV50770124;