rs559855953

chr3-121993371-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001199799.2(ILDR1):c.1378G>A(p.Gly460Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,610,884 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (3 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0680

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043005943).
• BP6: Variant 3-121993371-C-T is Benign according to our data. Variant chr3-121993371-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ILDR1	NM_001199799.2	c.1378G>A	p.Gly460Arg	missense_variant	7/8	ENST00000344209.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILDR1	ENST00000344209.10	c.1378G>A	p.Gly460Arg	missense_variant	7/8	1	NM_001199799.2	P2

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000354 AC: 88 AN: 248672 Hom.: 1 AF XY: 0.000483 AC XY: 65 AN XY: 134664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00193

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000213 AC: 311 AN: 1458580 Hom.: 3 Cov.: 41 AF XY: 0.000270 AC XY: 196 AN XY: 724928

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00181

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000113

Gnomad4 OTH exome AF: 0.000249

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20 AN XY: 74476

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000346 AC: 42

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jul 14, 2015

p.Gly460Arg in exon 7 of ILDR1: This variant is not expected to have clinical si gnificance because the glycine (Gly) residue at position 460 is not conserved th rough species, with >10 mammals having an arginine (Arg) at this position. It ha s been identified in 0.2% (28/16256) of South Asian chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs559855953). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.42
Dann	Benign	0.59
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.59	T;.;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.0043	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.95	N;N;.;N
REVEL	Benign	0.050
Sift	Benign	0.34	T;T;.;T
Sift4G	Benign	0.28	T;T;.;T
Polyphen		0.0	B;B;B;B
Vest4		0.10
MutPred		0.25		.;Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);.;
MVP		0.38
MPC		0.044
ClinPred		0.0064	T
GERP RS		-2.9
Varity_R		0.038
gMVP		0.081

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: rs559855953; hg19: chr3-121712218; COSMIC: COSV105083771;