chr3-122005271-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BS1_Supporting

The NM_001199799.2(ILDR1):c.352C>T(p.Arg118Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,562,362 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 2.20

Publications

0 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28080943).

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000473 (67/1415544) while in subpopulation AMR AF = 0.00144 (62/43186). AF 95% confidence interval is 0.00115. There are 1 homozygotes in GnomAdExome4. There are 30 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.352C>T	p.Arg118Trp	missense	Exon 3 of 8	NP_001186728.1	Q86SU0-1
ILDR1	NM_175924.4		c.352C>T	p.Arg118Trp	missense	Exon 3 of 7	NP_787120.1	Q86SU0-2
ILDR1	NM_001199800.2		c.352C>T	p.Arg118Trp	missense	Exon 3 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.352C>T	p.Arg118Trp	missense	Exon 3 of 8	ENSP00000345667.5	Q86SU0-1
ILDR1	ENST00000273691.7	TSL:1	c.352C>T	p.Arg118Trp	missense	Exon 3 of 7	ENSP00000273691.3	Q86SU0-2
ILDR1	ENST00000393631.5	TSL:1	c.352C>T	p.Arg118Trp	missense	Exon 3 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes

AF:

0.0000272

AC:

AN:

146818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000206

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:

0.000490

GnomAD2 exomes

AF:

0.000199

AC:

AN:

251062

AF XY:

0.000177

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00145

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:

0.0000473

AC:

AN:

1415544

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

703818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31976

American (AMR)

AF:

0.00144

AC:

AN:

43186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24408

East Asian (EAS)

AF:

0.00

AC:

AN:

36670

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

9.24e-7

AC:

AN:

1082216

Other (OTH)

AF:

0.0000525

AC:

AN:

57182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000272

AC:

AN:

146818

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39608

American (AMR)

AF:

0.000206

AC:

AN:

14576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4746

South Asian (SAS)

AF:

0.00

AC:

AN:

4448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67220

Other (OTH)

AF:

0.000490

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.0000412

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.0

PhyloP100

2.2

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.73

MutPred

0.43

Gain of ubiquitination at K121 (P = 0.0369)

MVP

0.68

MPC

0.29

ClinPred

0.35

GERP RS

3.8

Varity_R

0.76

gMVP

0.69

Mutation Taster

=21/79

disease causing

(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