rs144519399

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001199799.2(ILDR1):c.764C>T(p.Pro255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,536,070 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts 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. P255S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0036 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 31 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.83

Publications

5 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=0.0057062805).

BP6

Variant 3-121994196-G-A is Benign according to our data. Variant chr3-121994196-G-A is described in ClinVar as Benign. ClinVar VariationId is 505352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00356 (542/152268) while in subpopulation EAS AF = 0.00792 (41/5180). AF 95% confidence interval is 0.006. There are 6 homozygotes in GnomAd4. There are 353 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR1	NM_001199799.2 link	c.764C>T	p.Pro255Leu	missense_variant	Exon 6 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.764C>T	p.Pro255Leu	missense_variant	Exon 6 of 8	1	NM_001199799.2	ENSP00000345667.5		Q86SU0-1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00790

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0331

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00268

AC:

367

AN:

137134

AF XY:

0.00278

show subpopulations

Gnomad AFR exome

AF:

0.000621

Gnomad AMR exome

AF:

0.000613

Gnomad ASJ exome

AF:

0.000724

Gnomad EAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00357

GnomAD4 exome

AF:

0.00219

AC:

3024

AN:

1383802

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1428

AN XY:

682852

show subpopulations

African (AFR)

AF:

0.000633

AC:

AN:

31594

American (AMR)

AF:

0.000476

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.000635

AC:

AN:

25178

East Asian (EAS)

AF:

0.0122

AC:

436

AN:

35732

South Asian (SAS)

AF:

0.000290

AC:

AN:

79230

European-Finnish (FIN)

AF:

0.0339

AC:

1150

AN:

33902

Middle Eastern (MID)

AF:

0.000527

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00111

AC:

1198

AN:

1078866

Other (OTH)

AF:

0.00278

AC:

161

AN:

57908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

158

316

473

631

789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00356

AC:

542

AN:

152268

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00792

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0331

AC:

351

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00153

AC:

104

AN:

68016

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.000831

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.00281

AC:

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 19, 2018

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 specified

Benign:1

Oct 06, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro255Leu in exon 6 of ILDR1: This variant is not expected to have clinical si gnificance because it has been identified in 3.3% (52/1586) of Finnish chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs144519399). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.77

.;T;T

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.9

L;L;.

PhyloP100

2.8

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.0

D;.;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.026

D;.;T

Sift4G

Uncertain

0.041

D;.;T

Polyphen

0.057

B;B;B

Vest4

0.24

MVP

0.90

MPC

0.29

ClinPred

0.034

GERP RS

3.2

Varity_R

0.13

gMVP

0.73

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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