chr3-121994196-G-A

Position:

chr3-121994196-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000344209.10(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
ENST00000344209.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.83

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 -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 id is 505352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-121994196-G-A is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILDR1	NM_001199799.2 linkuse as main transcript	c.764C>T	p.Pro255Leu	missense_variant	6/8	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.764C>T	p.Pro255Leu	missense_variant	6/8	1	NM_001199799.2	ENSP00000345667	P2	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

GnomAD3 exomes

AF:

0.00268

AC:

367

AN:

137134

Hom.:

AF XY:

0.00278

AC XY:

207

AN XY:

74524

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 SAS exome

AF:

0.000267

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

Gnomad4 AFR exome

AF:

0.000633

Gnomad4 AMR exome

AF:

0.000476

Gnomad4 ASJ exome

AF:

0.000635

Gnomad4 EAS exome

AF:

0.0122

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00356

AC:

542

AN:

152268

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00792

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0331

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00142

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 06, 2016

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

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;.

MutationTaster

Benign

1.0

D;D;D;D

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

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