rs1555903974

Variant names:

• chr22-23573387-GC-AT
• rs1555903974
• NM_020070.4:c.520_521delGCinsAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_020070.4(IGLL1):​c.520_521delGCinsAT​(p.Ala174Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.000597 in 161 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A174S) has been classified as Uncertain significance.

• Frequency: GnomAD MNV: 𝑓 0.00060 Genomes: not found (cov: 32)
• Consequence: IGLL1 NM_020070.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.140
• 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: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000224277 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP6: Variant 22-23573387-GC-AT is Benign according to our data. Variant chr22-23573387-GC-AT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 538826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGLL1	NM_020070.4	MANE Select	c.520_521delGCinsAT	p.Ala174Met	missense	N/A	NP_064455.1	P15814-1
	IGLL1	NM_001369906.1		c.523_524delGCinsAT	p.Ala175Met	missense	N/A	NP_001356835.1
	IGLL1	NM_152855.3		c.*149_*150delGCinsAT		3_prime_UTR	Exon 2 of 2	NP_690594.1	P15814-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGLL1	ENST00000330377.3	TSL:1 MANE Select	c.520_521delGCinsAT	p.Ala174Met	missense	N/A	ENSP00000329312.2	P15814-1
	IGLL1	ENST00000249053.3	TSL:1	c.*149_*150delGCinsAT		3_prime_UTR	Exon 2 of 2	ENSP00000249053.3	P15814-2
	IGLL1	ENST00000438703.1	TSL:2	c.523_524delGCinsAT	p.Ala175Met	missense	N/A	ENSP00000403391.1	C9JEE0

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

GnomAD MNV AF: 0.000597 AC: 161 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Agammaglobulinemia 2, autosomal recessive (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555903974; hg19: chr22-23915574;