rs115649165

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS1

The NM_001199799.2(ILDR1):c.461C>T(p.Ser154Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000756 in 1,612,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00078 ( 0 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.14

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09402636).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000555 (84/151482) while in subpopulation NFE AF = 0.00106 (72/67938). AF 95% confidence interval is 0.000863. There are 0 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 31. 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.461C>T	p.Ser154Leu	missense	Exon 4 of 8	NP_001186728.1	Q86SU0-1
ILDR1	NM_175924.4		c.461C>T	p.Ser154Leu	missense	Exon 4 of 7	NP_787120.1	Q86SU0-2
ILDR1	NM_001199800.2		c.379+3461C>T		intron	N/A	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.461C>T	p.Ser154Leu	missense	Exon 4 of 8	ENSP00000345667.5	Q86SU0-1
ILDR1	ENST00000273691.7	TSL:1	c.461C>T	p.Ser154Leu	missense	Exon 4 of 7	ENSP00000273691.3	Q86SU0-2
ILDR1	ENST00000393631.5	TSL:1	c.379+3461C>T		intron	N/A	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes

AF:

0.000555

AC:

AN:

151366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

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:

0.00106

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000429

AC:

108

AN:

251484

AF XY:

0.000441

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000809

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000777

AC:

1136

AN:

1461424

Hom.:

Cov.:

AF XY:

0.000751

AC XY:

546

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33464

American (AMR)

AF:

0.000179

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.000243

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

0.000951

AC:

1057

AN:

1111942

Other (OTH)

AF:

0.000928

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<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:

0.000555

AC:

AN:

151482

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

AN XY:

73954

show subpopulations

African (AFR)

AF:

0.000267

AC:

AN:

41236

American (AMR)

AF:

0.0000658

AC:

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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:

0.000673

Hom.:

Bravo

AF:

0.000487

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hearing impairment (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.081

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.012

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.9

PhyloP100

4.1

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.10

Sift

Uncertain

0.019

Sift4G

Benign

0.070

Polyphen

0.78

Vest4

0.43

MVP

0.73

MPC

0.27

ClinPred

0.076

GERP RS

5.1

Varity_R

0.26

gMVP

0.40

Mutation Taster

=60/40

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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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