dbSNP rs114285337: IGLL1:p.Gln103Gln (chr22-23574980-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020070.4(IGLL1):c.309G>A(p.Gln103Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,612,656 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 8 hom. )

Consequence

IGLL1
NM_020070.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.198

Publications

1 publications found

Variant links:

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

IGLL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-23574980-C-T is Benign according to our data. Variant chr22-23574980-C-T is described in ClinVar as Benign. ClinVar VariationId is 538830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.198 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00578 (881/152294) while in subpopulation AFR AF = 0.0203 (843/41560). AF 95% confidence interval is 0.0191. There are 9 homozygotes in GnomAd4. There are 417 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 Unknown,AR,AD gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGLL1	NM_020070.4	MANE Select	c.309G>A	p.Gln103Gln	synonymous	Exon 2 of 3	NP_064455.1	P15814-1
IGLL1	NM_001369906.1		c.312G>A	p.Gln104Gln	synonymous	Exon 2 of 3	NP_001356835.1
IGLL1	NM_152855.3		c.207-1395G>A		intron	N/A	NP_690594.1	P15814-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGLL1	ENST00000330377.3	TSL:1 MANE Select	c.309G>A	p.Gln103Gln	synonymous	Exon 2 of 3	ENSP00000329312.2	P15814-1
IGLL1	ENST00000249053.3	TSL:1	c.207-1395G>A		intron	N/A	ENSP00000249053.3	P15814-2
IGLL1	ENST00000438703.1	TSL:2	c.312G>A	p.Gln104Gln	synonymous	Exon 2 of 3	ENSP00000403391.1	C9JEE0

Frequencies

GnomAD3 genomes

AF:

0.00580

AC:

882

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00146

AC:

367

AN:

251446

AF XY:

0.00112

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000607

AC:

886

AN:

1460362

Hom.:

Cov.:

AF XY:

0.000522

AC XY:

379

AN XY:

726608

show subpopulations

African (AFR)

AF:

0.0226

AC:

753

AN:

33362

American (AMR)

AF:

0.000827

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110700

Other (OTH)

AF:

0.00138

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00578

AC:

881

AN:

152294

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

417

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0203

AC:

843

AN:

41560

American (AMR)

AF:

0.00176

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00677

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Agammaglobulinemia 2, autosomal recessive (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.1

(source)

DANN

Benign

0.66

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over