3-121993204-A-C

Position:

• chr3-121993204-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001199799.2(ILDR1):​c.1545T>G​(p.Leu515=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,612,864 control chromosomes in the GnomAD database, including 433,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42118 hom., cov: 33)
  • Exomes 𝑓: 0.73 (391494 hom.)
• Consequence: ILDR1 NM_001199799.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.604

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-121993204-A-C is Benign according to our data. Variant chr3-121993204-A-C is described in ClinVar as [Benign]. Clinvar id is 44141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-121993204-A-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.604 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ILDR1	NM_001199799.2	c.1545T>G	p.Leu515=	synonymous_variant	7/8	ENST00000344209.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILDR1	ENST00000344209.10	c.1545T>G	p.Leu515=	synonymous_variant	7/8	1	NM_001199799.2	P2

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112440 AN: 152050 Hom.: 42078 Cov.: 33

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.703

GnomAD3 exomes AF: 0.726 AC: 179987 AN: 247786 Hom.: 66217 AF XY: 0.729 AC XY: 97823 AN XY: 134202

Gnomad AFR exome AF: 0.820

Gnomad AMR exome AF: 0.581

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.927

Gnomad SAS exome AF: 0.784

Gnomad FIN exome AF: 0.724

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.730 AC: 1066660 AN: 1460696 Hom.: 391494 Cov.: 59 AF XY: 0.732 AC XY: 531559 AN XY: 726598

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.938

Gnomad4 SAS exome AF: 0.780

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.724

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.740 AC: 112530 AN: 152168 Hom.: 42118 Cov.: 33 AF XY: 0.737 AC XY: 54851 AN XY: 74380

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.709

Alfa AF: 0.712 Hom.: 49540

Bravo AF: 0.734

Asia WGS AF: 0.868 AC: 3017 AN: 3478

EpiCase AF: 0.710

EpiControl AF: 0.706

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 02, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Leu515Leu in Exon 07 of ILDR1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 28.8% (2021/7018) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2877561). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 42 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs2877561; hg19: chr3-121712051; COSMIC: COSV56552211;