Variant rs201800585 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001369906.1(IGLL1):c.207-6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,598,610 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 6 hom. )

Consequence

IGLL1
NM_001369906.1 splice_region, intron

Scores

Splicing: ADA: 0.2458

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.681

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 22-23575091-A-T is Benign according to our data. Variant chr22-23575091-A-T is described in ClinVar as [Benign]. Clinvar id is 538831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
IGLL1	NM_020070.4 link	c.207-9T>A	intron_variant	ENST00000330377.3	NP_064455.1	P15814-1
IGLL1	NM_001369906.1 link	c.207-6T>A	splice_region_variant, intron_variant		NP_001356835.1
IGLL1	NM_152855.3 link	c.207-1506T>A	intron_variant		NP_690594.1	P15814-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
IGLL1	ENST00000330377.3 link	c.207-9T>A	intron_variant	1	NM_020070.4	ENSP00000329312.2	P15814-1
IGLL1	ENST00000249053.3 link	c.207-1506T>A	intron_variant	1		ENSP00000249053.3	P15814-2
IGLL1	ENST00000438703.1 link	c.207-6T>A	splice_region_variant, intron_variant	2		ENSP00000403391.1	C9JEE0

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

200

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00224

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00153

AC:

385

AN:

250946

Hom.:

AF XY:

0.00152

AC XY:

206

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.000620

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00272

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00151

AC:

2188

AN:

1446586

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1041

AN XY:

720568

show subpopulations

Gnomad4 AFR exome

AF:

0.000815

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00173

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00117

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00135

GnomAD4 genome

AF:

0.00132

AC:

200

AN:

152024

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Agammaglobulinemia 2, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.7

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.25

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