NM_001199799.2:c.791C>G

Variant names:

• chr3-121993958-G-C
• rs3915061
• NM_001199799.2:c.791C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001199799.2(ILDR1):​c.791C>G​(p.Pro264Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,609,260 control chromosomes in the GnomAD database, including 67,047 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P264Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.31 (7876 hom., cov: 32)
  • Exomes 𝑓: 0.28 (59171 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0750
• Publications: 30 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 42

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0229816E-4).
• BP6: Variant 3-121993958-G-C is Benign according to our data. Variant chr3-121993958-G-C is described in ClinVar as Benign. ClinVar VariationId is 44145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199799.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	NM_001199799.2	MANE Select	c.791C>G	p.Pro264Arg	missense	Exon 7 of 8	NP_001186728.1
	ILDR1	NM_175924.4		c.659C>G	p.Pro220Arg	missense	Exon 6 of 7	NP_787120.1
	ILDR1	NM_001199800.2		c.524C>G	p.Pro175Arg	missense	Exon 5 of 6	NP_001186729.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	ENST00000344209.10	TSL:1 MANE Select	c.791C>G	p.Pro264Arg	missense	Exon 7 of 8	ENSP00000345667.5
	ILDR1	ENST00000273691.7	TSL:1	c.659C>G	p.Pro220Arg	missense	Exon 6 of 7	ENSP00000273691.3
	ILDR1	ENST00000393631.5	TSL:1	c.524C>G	p.Pro175Arg	missense	Exon 5 of 6	ENSP00000377251.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47355 AN: 151876 Hom.: 7867 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.313 AC: 76764 AN: 245644 AF XY: 0.317

Gnomad AFR exome AF: 0.408

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.277 AC: 404264 AN: 1457266 Hom.: 59171 Cov.: 40 AF XY: 0.284 AC XY: 205711 AN XY: 725016

African (AFR) AF: 0.412 AC: 13768 AN: 33456

American (AMR) AF: 0.334 AC: 14936 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 8090 AN: 26126

East Asian (EAS) AF: 0.200 AC: 7935 AN: 39694

South Asian (SAS) AF: 0.477 AC: 41140 AN: 86230

European-Finnish (FIN) AF: 0.310 AC: 15392 AN: 49694

Middle Eastern (MID) AF: 0.338 AC: 1950 AN: 5766

European-Non Finnish (NFE) AF: 0.255 AC: 283189 AN: 1111282

Other (OTH) AF: 0.296 AC: 17864 AN: 60340

GnomAD4 genome AF: 0.312 AC: 47396 AN: 151994 Hom.: 7876 Cov.: 32 AF XY: 0.318 AC XY: 23590 AN XY: 74272

African (AFR) AF: 0.400 AC: 16584 AN: 41414

American (AMR) AF: 0.300 AC: 4579 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1136 AN: 5176

South Asian (SAS) AF: 0.486 AC: 2338 AN: 4810

European-Finnish (FIN) AF: 0.301 AC: 3177 AN: 10568

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17655 AN: 67960

Other (OTH) AF: 0.326 AC: 688 AN: 2108

Alfa AF: 0.130 Hom.: 751

Bravo AF: 0.309

TwinsUK AF: 0.260 AC: 963

ALSPAC AF: 0.270 AC: 1039

ESP6500AA AF: 0.399 AC: 1760

ESP6500EA AF: 0.262 AC: 2253

ExAC AF: 0.313 AC: 38024

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro264Arg in Exon 07 of ILDR1: This variant is not expected to have clinical sig nificance because it has been identified in 39.8% (1489/3738) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs3915061).

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Autosomal recessive nonsyndromic hearing loss 42 Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.6
DANN	Benign	0.24
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.00020	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.3	N
PhyloP100		-0.075
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.093
Sift	Benign	0.92	T
Sift4G	Benign	0.91	T
Polyphen		0.0010	B
Vest4		0.073
MPC		0.041
ClinPred		0.00043	T
GERP RS		0.99
Varity_R		0.050
gMVP		0.32
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3915061; hg19: chr3-121712805; COSMIC: COSV56550010;