22-23573153-T-G

Variant names:

• chr22-23573153-T-G
• rs1064417
• NM_020070.4:c.*113A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020070.4(IGLL1):​c.*113A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 907,458 control chromosomes in the GnomAD database, including 32,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4325 hom., cov: 31)
  • Exomes 𝑓: 0.26 (28355 hom.)
• Consequence: IGLL1 NM_020070.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.198
• Publications: 9 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

ENSG00000224277 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 22-23573153-T-G is Benign according to our data. Variant chr22-23573153-T-G is described in ClinVar as [Benign]. Clinvar id is 1262879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGLL1	NM_020070.4	c.*113A>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000330377.3	NP_064455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGLL1	ENST00000330377.3	c.*113A>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_020070.4	ENSP00000329312.2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31884 AN: 151798 Hom.: 4327 Cov.: 31

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.261 AC: 197115 AN: 755546 Hom.: 28355 Cov.: 10 AF XY: 0.259 AC XY: 102790 AN XY: 397242

African (AFR) AF: 0.0577 AC: 1081 AN: 18746

American (AMR) AF: 0.158 AC: 4977 AN: 31402

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 6309 AN: 18274

East Asian (EAS) AF: 0.0255 AC: 927 AN: 36374

South Asian (SAS) AF: 0.185 AC: 11740 AN: 63354

European-Finnish (FIN) AF: 0.236 AC: 11833 AN: 50162

Middle Eastern (MID) AF: 0.296 AC: 813 AN: 2748

European-Non Finnish (NFE) AF: 0.302 AC: 150189 AN: 498120

Other (OTH) AF: 0.254 AC: 9246 AN: 36366

GnomAD4 genome AF: 0.210 AC: 31873 AN: 151912 Hom.: 4325 Cov.: 31 AF XY: 0.205 AC XY: 15257 AN XY: 74266

African (AFR) AF: 0.0604 AC: 2502 AN: 41404

American (AMR) AF: 0.199 AC: 3039 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1160 AN: 3464

East Asian (EAS) AF: 0.0362 AC: 187 AN: 5162

South Asian (SAS) AF: 0.168 AC: 808 AN: 4814

European-Finnish (FIN) AF: 0.251 AC: 2650 AN: 10572

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20706 AN: 67912

Other (OTH) AF: 0.235 AC: 496 AN: 2108

Alfa AF: 0.210 Hom.: 1440

Bravo AF: 0.200

Asia WGS AF: 0.0880 AC: 309 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs1064417; hg19: chr22-23915340;