Variant 22-23573290-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_020070.4(IGLL1):c.618G>A(p.Thr206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000836 in 1,613,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 1 hom. )

Consequence

IGLL1
NM_020070.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.971

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-23573290-C-T is Benign according to our data. Variant chr22-23573290-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 538832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23573290-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.971 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGLL1	NM_020070.4 linkuse as main transcript	c.618G>A	p.Thr206=	synonymous_variant	3/3	ENST00000330377.3	NP_064455.1
IGLL1	NM_001369906.1 linkuse as main transcript	c.621G>A	p.Thr207=	synonymous_variant	3/3		NP_001356835.1
IGLL1	NM_152855.3 linkuse as main transcript	c.*247G>A		3_prime_UTR_variant	2/2		NP_690594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGLL1	ENST00000330377.3 linkuse as main transcript	c.618G>A	p.Thr206=	synonymous_variant	3/3	1	NM_020070.4	ENSP00000329312	P1	P15814-1
IGLL1	ENST00000249053.3 linkuse as main transcript	c.*247G>A		3_prime_UTR_variant	2/2	1		ENSP00000249053		P15814-2
	ENST00000458318.2 linkuse as main transcript	n.391-175C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000824

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000740

AC:

186

AN:

251416

Hom.:

AF XY:

0.000640

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000906

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000817

AC:

1194

AN:

1461770

Hom.:

Cov.:

AF XY:

0.000803

AC XY:

584

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000905

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152222

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000824

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000701

Hom.:

Bravo

AF:

0.00113

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Agammaglobulinemia 2, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.42

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over