rs114285337

Variant names:

• chr22-23574980-C-G
• rs114285337
• NM_020070.4:c.309G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-23574980-C-G
• chr22-23574980-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020070.4(IGLL1):​c.309G>C​(p.Gln103His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q103R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGLL1 NM_020070.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07837665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGLL1	NM_020070.4	c.309G>C	p.Gln103His	missense_variant	Exon 2 of 3	ENST00000330377.3	NP_064455.1
IGLL1	NM_001369906.1	c.312G>C	p.Gln104His	missense_variant	Exon 2 of 3		NP_001356835.1
IGLL1	NM_152855.3	c.207-1395G>C		intron_variant	Intron 1 of 1		NP_690594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGLL1	ENST00000330377.3	c.309G>C	p.Gln103His	missense_variant	Exon 2 of 3	1	NM_020070.4	ENSP00000329312.2
IGLL1	ENST00000249053.3	c.207-1395G>C		intron_variant	Intron 1 of 1	1		ENSP00000249053.3
IGLL1	ENST00000438703.1	c.312G>C	p.Gln104His	missense_variant	Exon 2 of 3	2		ENSP00000403391.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.29	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.46	N;.
PhyloP100		0.20
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.069
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.17	T;.
Polyphen		0.0090	B;.
Vest4		0.12
MutPred		0.28		Loss of stability (P = 0.1299);.;
MVP		0.081
MPC		0.050
ClinPred		0.095	T
GERP RS		-2.1
Varity_R		0.48
gMVP		0.32
Mutation Taster		=89/11	polymorphism

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: rs114285337; hg19: chr22-23917167;