rs201800585

chr22-23575091-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020070.4(IGLL1):c.207-9T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,598,610 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (6 hom.)
• Consequence: IGLL1 NM_020070.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.2458
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.681

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 22-23575091-A-T is Benign according to our data. Variant chr22-23575091-A-T is described in ClinVar as [Benign]. Clinvar id is 538831.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGLL1	NM_020070.4	c.207-9T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000330377.3
IGLL1	NM_001369906.1	c.207-6T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
IGLL1	NM_152855.3	c.207-1506T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGLL1	ENST00000330377.3	c.207-9T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_020070.4	P1
IGLL1	ENST00000249053.3	c.207-1506T>A		intron_variant		1
IGLL1	ENST00000438703.1	c.207-6T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 200 AN: 151908 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00224

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00153 AC: 385 AN: 250946 Hom.: 1 AF XY: 0.00152 AC XY: 206 AN XY: 135678

Gnomad AFR exome AF: 0.000620

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00272

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00151 AC: 2188 AN: 1446586 Hom.: 6 Cov.: 28 AF XY: 0.00144 AC XY: 1041 AN XY: 720568

Gnomad4 AFR exome AF: 0.000815

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00173

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00117

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.00132 AC: 200 AN: 152024 Hom.: 0 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74314

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00224

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00181 Hom.: 0

Bravo AF: 0.00118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Agammaglobulinemia 2, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.7
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.25
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: rs201800585; hg19: chr22-23917278; COSMIC: COSV50769940; COSMIC: COSV50769940;