rs1064419

Positions:

Variant summary

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

The NM_020070.4(IGLL1):c.521C>T(p.Ala174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,561,168 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A174T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0053 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

IGLL1
NM_020070.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.140

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039779544).

BP6

Variant 22-23573387-G-A is Benign according to our data. Variant chr22-23573387-G-A is described in ClinVar as [Benign]. Clinvar id is 580208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGLL1	NM_020070.4 linkuse as main transcript	c.521C>T	p.Ala174Val	missense_variant	3/3	ENST00000330377.3	NP_064455.1
IGLL1	NM_001369906.1 linkuse as main transcript	c.524C>T	p.Ala175Val	missense_variant	3/3		NP_001356835.1
IGLL1	NM_152855.3 linkuse as main transcript	c.*150C>T		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.521C>T	p.Ala174Val	missense_variant	3/3	1	NM_020070.4	ENSP00000329312	P1	P15814-1
IGLL1	ENST00000249053.3 linkuse as main transcript	c.*150C>T		3_prime_UTR_variant	2/2	1		ENSP00000249053		P15814-2
	ENST00000458318.2 linkuse as main transcript	n.391-78G>A		intron_variant, non_coding_transcript_variant		3
IGLL1	ENST00000438703.1 linkuse as main transcript	c.524C>T	p.Ala175Val	missense_variant	3/3	2		ENSP00000403391

Frequencies

GnomAD3 genomes

AF:

0.00531

AC:

788

AN:

148494

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00331

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00203

Gnomad EAS

AF:

0.00300

Gnomad SAS

AF:

0.00716

Gnomad FIN

AF:

0.00193

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00344

GnomAD3 exomes

AF:

0.00501

AC:

1198

AN:

239166

Hom.:

AF XY:

0.00446

AC XY:

579

AN XY:

129866

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.00172

Gnomad EAS exome

AF:

0.00683

Gnomad SAS exome

AF:

0.00378

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.00248

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00237

AC:

3343

AN:

1412576

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1692

AN XY:

703904

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.00958

Gnomad4 ASJ exome

AF:

0.00194

Gnomad4 EAS exome

AF:

0.00273

Gnomad4 SAS exome

AF:

0.00464

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.00159

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00533

AC:

792

AN:

148592

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

406

AN XY:

72594

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00203

Gnomad4 EAS

AF:

0.00300

Gnomad4 SAS

AF:

0.00716

Gnomad4 FIN

AF:

0.00193

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00390

Alfa

AF:

0.00341

Hom.:

ExAC

AF:

0.0385

AC:

4679

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 09, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.7

DANN

Benign

0.94

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.077

Sift

Benign

0.17

T;T

Sift4G

Benign

0.23

T;.

Polyphen

0.30

B;.

Vest4

0.030

MPC

0.062

ClinPred

0.010

GERP RS

-4.9

Varity_R

0.19

gMVP

0.32

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