3-121993364-C-G

Variant names:

• chr3-121993364-C-G
• rs200630651
• NM_001199799.2:c.1385G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001199799.2(ILDR1):​c.1385G>C​(p.Arg462Pro) 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 1,457,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3538398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR1	NM_001199799.2	c.1385G>C	p.Arg462Pro	missense_variant	Exon 7 of 8	ENST00000344209.10	NP_001186728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILDR1	ENST00000344209.10	c.1385G>C	p.Arg462Pro	missense_variant	Exon 7 of 8	1	NM_001199799.2	ENSP00000345667.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000805 AC: 2 AN: 248530 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134580

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: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457826 Hom.: 0 Cov.: 41 AF XY: 0.00000552 AC XY: 4 AN XY: 724418

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0027	.;T;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.66	T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.8	.;M;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.050	N;N;.;N
REVEL	Benign	0.15
Sift	Uncertain	0.025	D;T;.;D
Sift4G	Uncertain	0.057	T;T;.;T
Polyphen		0.97	D;D;D;D
Vest4		0.26
MutPred		0.31		.;Gain of glycosylation at R462 (P = 0.034);Gain of glycosylation at R462 (P = 0.034);.;
MVP		0.81
MPC		0.15
ClinPred		0.62	D
GERP RS		0.56
Varity_R		0.11
gMVP		0.28

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: rs200630651; hg19: chr3-121712211;