rs34883204

chr3-121993424-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.1325G>A(p.Arg442His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00728 in 1,613,804 control chromosomes in the GnomAD database, including 676 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict 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. R442C) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.037 (355 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (321 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.395

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=0.0022147894).
• BP6: Variant 3-121993424-C-T is Benign according to our data. Variant chr3-121993424-C-T is described in ClinVar as [Benign]. Clinvar id is 44139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ILDR1	NM_001199799.2	c.1325G>A	p.Arg442His	missense_variant	7/8	ENST00000344209.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILDR1	ENST00000344209.10	c.1325G>A	p.Arg442His	missense_variant	7/8	1	NM_001199799.2	P2

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5565 AN: 152156 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.00983 AC: 2455 AN: 249808 Hom.: 137 AF XY: 0.00755 AC XY: 1021 AN XY: 135256

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.00603

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000701

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00422 AC: 6166 AN: 1461530 Hom.: 321 Cov.: 40 AF XY: 0.00374 AC XY: 2716 AN XY: 727044

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.00716

Gnomad4 ASJ exome AF: 0.00969

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000489

Gnomad4 OTH exome AF: 0.00957

GnomAD4 genome AF: 0.0367 AC: 5588 AN: 152274 Hom.: 355 Cov.: 32 AF XY: 0.0357 AC XY: 2657 AN XY: 74464

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.00704 Hom.: 81

Bravo AF: 0.0421

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.120 AC: 528

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.0117 AC: 1415

Asia WGS AF: 0.00982 AC: 35 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Arg442His in Exon 07 of ILDR1: This variant is not expected to have clinical sig nificance because it has been identified in 12.3% (459/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34883204). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 23, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	5.4
Dann	Benign	0.96
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.79	T;.;T;T
MetaRNN	Benign	0.0022	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.76	P;P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N;N;.;N
REVEL	Benign	0.20
Sift	Benign	0.15	T;T;.;T
Sift4G	Uncertain	0.0070	D;D;.;D
Polyphen		0.0030	B;B;B;B
Vest4		0.12
MPC		0.046
ClinPred		0.0015	T
GERP RS		-0.55
Varity_R		0.066
gMVP		0.14

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

Other links and lift over

dbSNP: rs34883204; hg19: chr3-121712271;