rs140567004

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_001199799.2(ILDR1):c.1297C>T(p.Arg433Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R433Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6

Conservation

PhyloP100: 1.41

Publications

3 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: G2P, Labcorp Genetics (formerly Invitae)
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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005616069).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000512 (78/152326) while in subpopulation AFR AF = 0.00125 (52/41570). AF 95% confidence interval is 0.00098. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199799.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ILDR1	NM_001199799.2	MANE Select	c.1297C>T	p.Arg433Trp	missense	Exon 7 of 8	NP_001186728.1	Q86SU0-1
ILDR1	NM_175924.4		c.1165C>T	p.Arg389Trp	missense	Exon 6 of 7	NP_787120.1	Q86SU0-2
ILDR1	NM_001199800.2		c.1030C>T	p.Arg344Trp	missense	Exon 5 of 6	NP_001186729.1	Q86SU0-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ILDR1	ENST00000344209.10	TSL:1 MANE Select	c.1297C>T	p.Arg433Trp	missense	Exon 7 of 8	ENSP00000345667.5	Q86SU0-1
ILDR1	ENST00000273691.7	TSL:1	c.1165C>T	p.Arg389Trp	missense	Exon 6 of 7	ENSP00000273691.3	Q86SU0-2
ILDR1	ENST00000393631.5	TSL:1	c.1030C>T	p.Arg344Trp	missense	Exon 5 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000267

AC:

AN:

250626

AF XY:

0.000243

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000199

AC:

291

AN:

1461742

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33474

American (AMR)

AF:

0.000581

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000170

AC:

189

AN:

1111972

Other (OTH)

AF:

0.000381

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000512

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41570

American (AMR)

AF:

0.000915

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68032

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

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:

0.000285

Hom.:

Bravo

AF:

0.000555

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autosomal recessive nonsyndromic hearing loss 42 (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

PhyloP100

1.4

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.12

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.021

Polyphen

0.027

Vest4

0.25

MVP

0.70

MPC

0.11

ClinPred

0.045

GERP RS

-3.0

Varity_R

0.23

gMVP

0.20

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over