chr3-121993251-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001199799.2(ILDR1):c.1498C>T(p.His500Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,613,562 control chromosomes in the GnomAD database, including 673 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 353 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 320 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.05

Publications

8 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017394125).

BP6

Variant 3-121993251-G-A is Benign according to our data. Variant chr3-121993251-G-A is described in ClinVar as [Benign]. Clinvar id is 44140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR1	NM_001199799.2 link	c.1498C>T	p.His500Tyr	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.1498C>T	p.His500Tyr	missense_variant	Exon 7 of 8	1	NM_001199799.2	ENSP00000345667.5		Q86SU0-1

Frequencies

GnomAD3 genomes

AF:

0.0365

AC:

5559

AN:

152206

Hom.:

352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.00987

AC:

2446

AN:

247868

AF XY:

0.00755

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00601

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000689

Gnomad OTH exome

AF:

0.00499

GnomAD4 exome

AF:

0.00420

AC:

6136

AN:

1461238

Hom.:

320

Cov.:

AF XY:

0.00372

AC XY:

2703

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.131

AC:

4387

AN:

33466

American (AMR)

AF:

0.00714

AC:

319

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00969

AC:

253

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.000325

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000481

AC:

535

AN:

1111758

Other (OTH)

AF:

0.00960

AC:

579

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

314

629

943

1258

1572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0366

AC:

5582

AN:

152324

Hom.:

353

Cov.:

AF XY:

0.0355

AC XY:

2646

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.126

AC:

5251

AN:

41554

American (AMR)

AF:

0.0129

AC:

197

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00835

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68032

Other (OTH)

AF:

0.0260

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

259

518

778

1037

1296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00907

Hom.:

132

Bravo

AF:

0.0420

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.118

AC:

520

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0116

AC:

1407

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

His500Tyr in Exon 07 of ILDR1: This variant is not expected to have clinical sig nificance because it has been identified in 12.1% (450/3734) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34284625). -

Nov 15, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:3

May 23, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0060

.;T;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.53

T;.;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L;.

PhyloP100

2.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.56

N;N;.;N

REVEL

Benign

0.15

Sift

Benign

0.25

T;T;.;T

Sift4G

Benign

1.0

T;T;.;T

Polyphen

0.38

B;B;B;B

Vest4

0.085

MPC

0.044

ClinPred

0.0068

GERP RS

4.0

Varity_R

0.030

gMVP

0.075

Mutation Taster

=98/2

polymorphism (auto)

(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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chr3-121993251-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over