rs34284625

chr3-121993251-G-A

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.1498C>T(p.His500Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,613,562 control chromosomes in the GnomAD database, including 673 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (353 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (320 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.05

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=0.0017394125).
• BP6: Variant 3-121993251-G-A is Benign according to our data. Variant chr3-121993251-G-A is described in ClinVar as [Benign]. Clinvar id is 44140.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.1498C>T	p.His500Tyr	missense_variant	7/8	ENST00000344209.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILDR1	ENST00000344209.10	c.1498C>T	p.His500Tyr	missense_variant	7/8	1	NM_001199799.2	P2

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5559 AN: 152206 Hom.: 352 Cov.: 33

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: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.00987 AC: 2446 AN: 247868 Hom.: 138 AF XY: 0.00755 AC XY: 1016 AN XY: 134600

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.00601

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000689

Gnomad OTH exome AF: 0.00499

GnomAD4 exome AF: 0.00420 AC: 6136 AN: 1461238 Hom.: 320 Cov.: 40 AF XY: 0.00372 AC XY: 2703 AN XY: 726914

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.00714

Gnomad4 ASJ exome AF: 0.00969

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000481

Gnomad4 OTH exome AF: 0.00960

GnomAD4 genome AF: 0.0366 AC: 5582 AN: 152324 Hom.: 353 Cov.: 33 AF XY: 0.0355 AC XY: 2646 AN XY: 74492

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.00695 Hom.: 78

Bravo AF: 0.0420

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.118 AC: 520

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.0116 AC: 1407

Asia WGS AF: 0.00982 AC: 35 AN: 3478

EpiCase AF: 0.000654

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	PreventionGenetics, part of Exact Sciences	-	- -
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	His500Tyr in Exon 07 of ILDR1: This variant is not expected to have clinical sig nificance because it has been identified in 12.1% (450/3734) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34284625). -

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	0.068
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	13
Dann	Uncertain	0.99
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.53	T;.;T;T
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.56	N;N;.;N
REVEL	Benign	0.15
Sift	Benign	0.25	T;T;.;T
Sift4G	Benign	1.0	T;T;.;T
Polyphen		0.38	B;B;B;B
Vest4		0.085
MPC		0.044
ClinPred		0.0068	T
GERP RS		4.0
Varity_R		0.030
gMVP		0.075

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: rs34284625; hg19: chr3-121712098;