rs1553743343

chr3-121993612-C-Gchr3-121993612-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199799.2(ILDR1):c.1137G>C(p.Glu379Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,894 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.198

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=0.06695205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ILDR1	NM_001199799.2	c.1137G>C	p.Glu379Asp	missense_variant	7/8	ENST00000344209.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILDR1	ENST00000344209.10	c.1137G>C	p.Glu379Asp	missense_variant	7/8	1	NM_001199799.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461894 Hom.: 0 Cov.: 41 AF XY: 0.00000550 AC XY: 4 AN XY: 727248

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jul 11, 2017

Variant classified as Uncertain Significance - Favor Benign. The p.Glu379Asp var iant in ILDR1 has not been previously reported in individuals with hearing loss or in large population studies. The glutamic acid (Glu) at position 379 is not c onserved across mammals or evolutionary distant species, with 2 mammals (lesser Egyptian jerboa, star-nosed mole) having an aspartic acid (Asp), supporting that the change at this position may be tolerated. Additional computational predicti on tools suggest that this variant may not impact the protein, though this infor mation is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Glu379Asp variant is uncertain, available data s uggest that it is more likely to be benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	11
Dann	Uncertain	1.0
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.74	T;.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.067	T;T;T;T
MetaSVM	Benign	-0.66	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.030	N;N;.;N
REVEL	Benign	0.077
Sift	Uncertain	0.021	D;T;.;D
Sift4G	Benign	0.27	T;T;.;T
Polyphen		0.57	P;B;B;D
Vest4		0.19
MutPred		0.23		.;Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);.;
MVP		0.79
MPC		0.039
ClinPred		0.34	T
GERP RS		2.8
Varity_R		0.041
gMVP		0.14

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: rs1553743343; hg19: chr3-121712459;