3-121988101-C-CG

Variant names:

• chr3-121988101-C-CG
• rs371813355
• NM_001199799.2:c.*265dupC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001199799.2(ILDR1):​c.*265dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 527,646 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (1 hom.)
• Consequence: ILDR1 NM_001199799.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56
• Publications: 0 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

LOC101927010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00475 (722/152146) while in subpopulation AFR AF = 0.0165 (684/41510). AF 95% confidence interval is 0.0155. There are 8 homozygotes in GnomAd4. There are 338 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR1	NM_001199799.2	c.*265dupC		3_prime_UTR_variant	Exon 8 of 8	ENST00000344209.10	NP_001186728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILDR1	ENST00000344209.10	c.*265dupC		3_prime_UTR_variant	Exon 8 of 8	1	NM_001199799.2	ENSP00000345667.5
ILDR1	ENST00000273691.7	c.*265dupC		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000273691.3
ILDR1	ENST00000393631.5	c.*265dupC		downstream_gene_variant		1		ENSP00000377251.1
ILDR1	ENST00000460554.2	n.*244dupC		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 717 AN: 152028 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.000621 AC: 233 AN: 375500 Hom.: 1 Cov.: 0 AF XY: 0.000540 AC XY: 112 AN XY: 207484

African (AFR) AF: 0.0172 AC: 185 AN: 10768

American (AMR) AF: 0.000539 AC: 14 AN: 25968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13238

East Asian (EAS) AF: 0.00 AC: 0 AN: 18254

South Asian (SAS) AF: 0.00 AC: 0 AN: 54792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18772

Middle Eastern (MID) AF: 0.000647 AC: 1 AN: 1546

European-Non Finnish (NFE) AF: 0.0000282 AC: 6 AN: 212654

Other (OTH) AF: 0.00138 AC: 27 AN: 19508

GnomAD4 genome AF: 0.00475 AC: 722 AN: 152146 Hom.: 8 Cov.: 32 AF XY: 0.00454 AC XY: 338 AN XY: 74376

African (AFR) AF: 0.0165 AC: 684 AN: 41510

American (AMR) AF: 0.00150 AC: 23 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67992

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00470 Hom.: 2

Bravo AF: 0.00546

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 13, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs371813355; hg19: chr3-121706948;