3-121993170-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001199799.2(ILDR1):c.1579G>A(p.Gly527Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,606,632 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G527G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 3 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

2 publications found

Variant links:

Genes affected

ILDR1 (HGNC:28741): (immunoglobulin like domain containing receptor 1) This gene encodes a protein that contains an immunoglobulin-like domain. The encoded protein may function as a multimeric receptor at the cell surface. The expression of this gene may be a diagnostic marker for cancer progression. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ILDR1 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 42
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ILDR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25604594).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR1	NM_001199799.2 link	c.1579G>A	p.Gly527Arg	missense_variant	Exon 7 of 8	ENST00000344209.10	NP_001186728.1	Q86SU0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILDR1	ENST00000344209.10 link	c.1579G>A	p.Gly527Arg	missense_variant	Exon 7 of 8	1	NM_001199799.2	ENSP00000345667.5		Q86SU0-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000171

AC:

AN:

233886

AF XY:

0.00000791

show subpopulations

Gnomad AFR exome

AF:

0.0000674

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1454276

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

722678

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

43748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25968

East Asian (EAS)

AF:

0.00

AC:

AN:

39286

South Asian (SAS)

AF:

0.000224

AC:

AN:

84762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108506

Other (OTH)

AF:

0.00

AC:

AN:

60072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41588

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Apr 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1579G>A (p.G527R) alteration is located in exon 7 (coding exon 7) of the ILDR1 gene. This alteration results from a G to A substitution at nucleotide position 1579, causing the glycine (G) at amino acid position 527 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0093

.;T;T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

T;.;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Uncertain

-0.096

MutationAssessor

Uncertain

2.7

.;M;M;.

PhyloP100

1.7

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;N;.;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.0060

D;D;.;D

Sift4G

Uncertain

0.031

D;D;.;D

Polyphen

1.0

D;D;D;D

Vest4

0.39

MutPred

0.27

.;Gain of solvent accessibility (P = 2e-04);Gain of solvent accessibility (P = 2e-04);.;

MVP

0.82

MPC

0.30

ClinPred

0.49

GERP RS

5.8

Varity_R

0.17

gMVP

0.094

Mutation Taster

=81/19

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

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3-121993170-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over