rs1217446345

chr3-122022053-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001199799.2(ILDR1):c.25C>T(p.Pro9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.555

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11842832).
• BP6: Variant 3-122022053-G-A is Benign according to our data. Variant chr3-122022053-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 517153.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ILDR1	NM_001199799.2	c.25C>T	p.Pro9Ser	missense_variant	1/8	ENST00000344209.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILDR1	ENST00000344209.10	c.25C>T	p.Pro9Ser	missense_variant	1/8	1	NM_001199799.2	P2
ILDR1	ENST00000273691.7	c.25C>T	p.Pro9Ser	missense_variant	1/7	1		A2
ILDR1	ENST00000393631.5	c.25C>T	p.Pro9Ser	missense_variant	1/6	1
ILDR1	ENST00000642615.1	c.25C>T	p.Pro9Ser	missense_variant, NMD_transcript_variant	1/8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000829 AC: 2 AN: 241158 Hom.: 0 AF XY: 0.0000153 AC XY: 2 AN XY: 130962

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459026 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 23, 2016

p.Pro9Ser in exon 1 of ILDR1: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, 3 mammals (squirrel, jerboa, and Weddell seal) have a serine (Ser) at this po sition despite high nearby amino acid conservation. In addition, computational p rediction tools do not suggest a high likelihood of impact to the protein. It ha s also been identified in 2/106558 European chromosomes by the genome Aggregatio n Database (gnomAD , http://gnomad.broadinstitute.org/). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	14
Dann	Uncertain	0.99
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.63	T;.;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N;N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.31	N;N;.;N
REVEL	Benign	0.046
Sift	Benign	0.036	D;T;.;T
Sift4G	Benign	0.14	T;T;.;T
Polyphen		0.073	B;B;B;B
Vest4		0.16
MutPred		0.42		Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);
MVP		0.72
MPC		0.040
ClinPred		0.080	T
GERP RS		3.6
Varity_R		0.032
gMVP		0.64

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: rs1217446345; hg19: chr3-121740900;