3-121993444-G-T

Position:

chr3-121993444-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000344209.10(ILDR1):c.1305C>A(p.Ser435Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,614,008 control chromosomes in the GnomAD database, including 10 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 10 hom. )

Consequence

ILDR1
ENST00000344209.10 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.413

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006204456).

BP6

Variant 3-121993444-G-T is Benign according to our data. Variant chr3-121993444-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 504523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILDR1	NM_001199799.2 linkuse as main transcript	c.1305C>A	p.Ser435Arg	missense_variant	7/8	ENST00000344209.10	NP_001186728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILDR1	ENST00000344209.10 linkuse as main transcript	c.1305C>A	p.Ser435Arg	missense_variant	7/8	1	NM_001199799.2	ENSP00000345667	P2	Q86SU0-1

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

174

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00232

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00125

AC:

313

AN:

250092

Hom.:

AF XY:

0.00138

AC XY:

187

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00262

Gnomad OTH exome

AF:

0.000986

GnomAD4 exome

AF:

0.00222

AC:

3245

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

1554

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000450

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00114

AC:

174

AN:

152334

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00123

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00148

AC:

180

EpiCase

AF:

0.00213

EpiControl

AF:

0.00225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 13, 2017	p.Ser435Arg in exon 7 of ILDR1: This variant is not expected to have clinical si gnificance because it has been identified in 0.25% (315/125942) of European chro mosomes including 2 homozygotes by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org; dbSNP rs35597690). Furthermore, this amino acid re sidue is not conserved across species, including mammals. Of note, 7 mammals (pr airie vole, Chinese hamster, golden hamster, mouse, rat, pig, and sheep) have an arginine (Arg) at this position. -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 09, 2017	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. -

ILDR1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.9

DANN

Benign

0.88

DEOGEN2

Benign

0.0037

.;T;T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.60

T;.;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

.;L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.90

N;N;D;N

REVEL

Benign

0.056

Sift

Benign

0.11

T;T;D;T

Sift4G

Benign

0.30

T;T;.;T

Polyphen

0.0040

B;B;B;B

Vest4

0.12

MutPred

0.26

.;Loss of phosphorylation at S435 (P = 0.0011);Loss of phosphorylation at S435 (P = 0.0011);.;

MVP

0.61

MPC

0.043

ClinPred

0.0066

GERP RS

2.2

Varity_R

0.11

gMVP

0.078

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over