rs144519399

Positions:

• chr3-121994196-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001199799.2(ILDR1):​c.764C>T​(p.Pro255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,536,070 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (31 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.83

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057062805).
• BP6: Variant 3-121994196-G-A is Benign according to our data. Variant chr3-121994196-G-A is described in ClinVar as [Benign]. Clinvar id is 505352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-121994196-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00356 (542/152268) while in subpopulation EAS AF= 0.00792 (41/5180). AF 95% confidence interval is 0.006. There are 6 homozygotes in gnomad4. There are 353 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILDR1	NM_001199799.2	c.764C>T	p.Pro255Leu	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.764C>T	p.Pro255Leu	missense_variant	6/8	1	NM_001199799.2	ENSP00000345667.5

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 540 AN: 152150 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00268 AC: 367 AN: 137134 Hom.: 3 AF XY: 0.00278 AC XY: 207 AN XY: 74524

Gnomad AFR exome AF: 0.000621

Gnomad AMR exome AF: 0.000613

Gnomad ASJ exome AF: 0.000724

Gnomad EAS exome AF: 0.00199

Gnomad SAS exome AF: 0.000267

Gnomad FIN exome AF: 0.0337

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.00357

GnomAD4 exome AF: 0.00219 AC: 3024 AN: 1383802 Hom.: 31 Cov.: 33 AF XY: 0.00209 AC XY: 1428 AN XY: 682852

Gnomad4 AFR exome AF: 0.000633

Gnomad4 AMR exome AF: 0.000476

Gnomad4 ASJ exome AF: 0.000635

Gnomad4 EAS exome AF: 0.0122

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0339

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00278

GnomAD4 genome AF: 0.00356 AC: 542 AN: 152268 Hom.: 6 Cov.: 32 AF XY: 0.00474 AC XY: 353 AN XY: 74456

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00792

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.000831

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00130 AC: 5

ExAC AF: 0.00281 AC: 89

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 06, 2016

p.Pro255Leu in exon 6 of ILDR1: This variant is not expected to have clinical si gnificance because it has been identified in 3.3% (52/1586) of Finnish chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs144519399). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.057
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.77	.;T;T
MetaRNN	Benign	0.0057	T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.0	D;.;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.026	D;.;T
Sift4G	Uncertain	0.041	D;.;T
Polyphen		0.057	B;B;B
Vest4		0.24
MVP		0.90
MPC		0.29
ClinPred		0.034	T
GERP RS		3.2
Varity_R		0.13
gMVP		0.73

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: rs144519399; hg19: chr3-121713043;