rs34883204

Variant names:

• chr3-121993424-C-T
• rs34883204
• NM_001199799.2:c.1325G>A

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.1325G>A​(p.Arg442His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00728 in 1,613,804 control chromosomes in the GnomAD database, including 676 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. R442C) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.037 (355 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (321 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.395
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae)
• 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=0.0022147894).
• BP6: Variant 3-121993424-C-T is Benign according to our data. Variant chr3-121993424-C-T is described in ClinVar as Benign. ClinVar VariationId is 44139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	NM_001199799.2	MANE Select	c.1325G>A	p.Arg442His	missense	Exon 7 of 8	NP_001186728.1	Q86SU0-1
	ILDR1	NM_175924.4		c.1193G>A	p.Arg398His	missense	Exon 6 of 7	NP_787120.1	Q86SU0-2
	ILDR1	NM_001199800.2		c.1058G>A	p.Arg353His	missense	Exon 5 of 6	NP_001186729.1	Q86SU0-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	ENST00000344209.10	TSL:1 MANE Select	c.1325G>A	p.Arg442His	missense	Exon 7 of 8	ENSP00000345667.5	Q86SU0-1
	ILDR1	ENST00000273691.7	TSL:1	c.1193G>A	p.Arg398His	missense	Exon 6 of 7	ENSP00000273691.3	Q86SU0-2
	ILDR1	ENST00000393631.5	TSL:1	c.1058G>A	p.Arg353His	missense	Exon 5 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5565 AN: 152156 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0268

GnomAD2 exomes AF: 0.00983 AC: 2455 AN: 249808 AF XY: 0.00755

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.00603

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000701

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00422 AC: 6166 AN: 1461530 Hom.: 321 Cov.: 40 AF XY: 0.00374 AC XY: 2716 AN XY: 727044

African (AFR) AF: 0.132 AC: 4406 AN: 33474

American (AMR) AF: 0.00716 AC: 320 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00969 AC: 253 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000489 AC: 544 AN: 1111868

Other (OTH) AF: 0.00957 AC: 578 AN: 60370

GnomAD4 genome AF: 0.0367 AC: 5588 AN: 152274 Hom.: 355 Cov.: 32 AF XY: 0.0357 AC XY: 2657 AN XY: 74464

African (AFR) AF: 0.127 AC: 5256 AN: 41538

American (AMR) AF: 0.0129 AC: 197 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68026

Other (OTH) AF: 0.0265 AC: 56 AN: 2114

Alfa AF: 0.00832 Hom.: 118

Bravo AF: 0.0421

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.120 AC: 528

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.0117 AC: 1415

Asia WGS AF: 0.00982 AC: 35 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.4
DANN	Benign	0.96
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.83	L
PhyloP100		-0.40
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.0030	B
Vest4		0.12
MPC		0.046
ClinPred		0.0015	T
GERP RS		-0.55
Varity_R		0.066
gMVP		0.14
Mutation Taster		=98/2	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: rs34883204; hg19: chr3-121712271;