rs182963279

Positions:

• chr3-121994299-G-A
• chr3-121994299-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001199799.2(ILDR1):​c.661C>T​(p.Arg221Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000189 in 1,535,156 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 4.54

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012668848).
• BP6: Variant 3-121994299-G-A is Benign according to our data. Variant chr3-121994299-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 505909.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILDR1	NM_001199799.2	c.661C>T	p.Arg221Cys	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	c.661C>T	p.Arg221Cys	missense_variant	6/8	1	NM_001199799.2	ENSP00000345667.5

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.000587 AC: 80 AN: 136348 Hom.: 0 AF XY: 0.000553 AC XY: 41 AN XY: 74134

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000164

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000190

Gnomad SAS exome AF: 0.00293

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000749

Gnomad OTH exome AF: 0.000960

GnomAD4 exome AF: 0.000177 AC: 245 AN: 1382830 Hom.: 2 Cov.: 32 AF XY: 0.000205 AC XY: 140 AN XY: 682210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000308

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.00234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000186

Gnomad4 OTH exome AF: 0.000467

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31 AN XY: 74494

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.0000516 Hom.: 0

Bravo AF: 0.000491

ExAC AF: 0.000950 AC: 20

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2021	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 24, 2023	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 22, 2017

p.Arg221Cys in exon 6 of ILDR1: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (65/22550) of South Asian chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs182963279). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.013	T;T;T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.1	D;.;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.011	D;.;T
Sift4G	Pathogenic	0.0010	D;.;D
Polyphen		1.0	D;D;D
Vest4		0.62
MVP		0.94
MPC		0.13
ClinPred		0.099	T
GERP RS		5.1
Varity_R		0.16
gMVP		0.59

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: rs182963279; hg19: chr3-121713146; COSMIC: COSV56547827;