22-23580170-C-T

Variant names:

• chr22-23580170-C-T
• rs1044209410
• NM_020070.4:c.21G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_020070.4(IGLL1):​c.21G>A​(p.Gln7Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,391,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: IGLL1 NM_020070.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• agammaglobulinemia 2, autosomal recessive

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020070.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGLL1	NM_020070.4	MANE Select	c.21G>A	p.Gln7Gln	synonymous	Exon 1 of 3	NP_064455.1
	IGLL1	NM_001369906.1		c.21G>A	p.Gln7Gln	synonymous	Exon 1 of 3	NP_001356835.1
	IGLL1	NM_152855.3		c.21G>A	p.Gln7Gln	synonymous	Exon 1 of 2	NP_690594.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGLL1	ENST00000330377.3	TSL:1 MANE Select	c.21G>A	p.Gln7Gln	synonymous	Exon 1 of 3	ENSP00000329312.2
	IGLL1	ENST00000249053.3	TSL:1	c.21G>A	p.Gln7Gln	synonymous	Exon 1 of 2	ENSP00000249053.3
	IGLL1	ENST00000438703.1	TSL:2	c.21G>A	p.Gln7Gln	synonymous	Exon 1 of 3	ENSP00000403391.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1391300 Hom.: 0 Cov.: 31 AF XY: 0.00000291 AC XY: 2 AN XY: 686890

African (AFR) AF: 0.00 AC: 0 AN: 31946

American (AMR) AF: 0.00 AC: 0 AN: 35822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 36306

South Asian (SAS) AF: 0.00 AC: 0 AN: 79388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4712

European-Non Finnish (NFE) AF: 0.00000463 AC: 5 AN: 1080148

Other (OTH) AF: 0.0000173 AC: 1 AN: 57938

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		0.38
PromoterAI		0.014	Neutral

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

Other links and lift over

dbSNP: rs1044209410; hg19: chr22-23922357;