rs35906279

Positions:

• chr3-121993451-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001199799.2(ILDR1):​c.1298G>A​(p.Arg433Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,614,048 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (109 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (86 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.517

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021483302).
• BP6: Variant 3-121993451-C-T is Benign according to our data. Variant chr3-121993451-C-T is described in ClinVar as [Benign]. Clinvar id is 44138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILDR1	NM_001199799.2	c.1298G>A	p.Arg433Gln	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	c.1298G>A	p.Arg433Gln	missense_variant	7/8	1	NM_001199799.2	ENSP00000345667	P2

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2863 AN: 152172 Hom.: 109 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00486 AC: 1217 AN: 250586 Hom.: 41 AF XY: 0.00370 AC XY: 501 AN XY: 135552

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00188 AC: 2754 AN: 1461760 Hom.: 86 Cov.: 41 AF XY: 0.00166 AC XY: 1207 AN XY: 727170

Gnomad4 AFR exome AF: 0.0679

Gnomad4 AMR exome AF: 0.00288

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000854

Gnomad4 OTH exome AF: 0.00364

GnomAD4 genome AF: 0.0188 AC: 2865 AN: 152288 Hom.: 109 Cov.: 32 AF XY: 0.0180 AC XY: 1342 AN XY: 74484

Gnomad4 AFR AF: 0.0649

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00813 Hom.: 24

Bravo AF: 0.0215

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0695 AC: 306

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00617 AC: 749

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Arg433Gln in Exon 07 of ILDR1: This variant is not expected to have clinical sig nificance because it has been identified in 6.9% (259/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs35906279). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	.;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.64	T;.;T;T
MetaRNN	Benign	0.0021	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;M;M;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.1	N;N;.;N
REVEL	Benign	0.045
Sift	Benign	0.031	D;D;.;D
Sift4G	Benign	0.097	T;T;.;T
Polyphen		0.10	B;B;B;B
Vest4		0.19
MVP		0.60
MPC		0.044
ClinPred		0.020	T
GERP RS		0.57
Varity_R		0.050
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs35906279; hg19: chr3-121712298;