rs2877561

Variant names:

• chr3-121993204-A-C
• rs2877561
• NM_001199799.2:c.1545T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-121993204-A-C
• chr3-121993204-A-G
• chr3-121993204-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001199799.2(ILDR1):​c.1545T>G​(p.Leu515Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,612,864 control chromosomes in the GnomAD database, including 433,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42118 hom., cov: 33)
  • Exomes 𝑓: 0.73 (391494 hom.)
• Consequence: ILDR1 NM_001199799.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.604
• Publications: 36 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-121993204-A-C is Benign according to our data. Variant chr3-121993204-A-C is described in ClinVar as Benign. ClinVar VariationId is 44141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.604 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 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.1545T>G	p.Leu515Leu	synonymous	Exon 7 of 8	NP_001186728.1	Q86SU0-1
	ILDR1	NM_175924.4		c.1413T>G	p.Leu471Leu	synonymous	Exon 6 of 7	NP_787120.1	Q86SU0-2
	ILDR1	NM_001199800.2		c.1278T>G	p.Leu426Leu	synonymous	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.1545T>G	p.Leu515Leu	synonymous	Exon 7 of 8	ENSP00000345667.5	Q86SU0-1
	ILDR1	ENST00000273691.7	TSL:1	c.1413T>G	p.Leu471Leu	synonymous	Exon 6 of 7	ENSP00000273691.3	Q86SU0-2
	ILDR1	ENST00000393631.5	TSL:1	c.1278T>G	p.Leu426Leu	synonymous	Exon 5 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112440 AN: 152050 Hom.: 42078 Cov.: 33

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.703

GnomAD2 exomes AF: 0.726 AC: 179987 AN: 247786 AF XY: 0.729

Gnomad AFR exome AF: 0.820

Gnomad AMR exome AF: 0.581

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.927

Gnomad FIN exome AF: 0.724

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.730 AC: 1066660 AN: 1460696 Hom.: 391494 Cov.: 59 AF XY: 0.732 AC XY: 531559 AN XY: 726598

African (AFR) AF: 0.820 AC: 27436 AN: 33470

American (AMR) AF: 0.583 AC: 25944 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 17649 AN: 26110

East Asian (EAS) AF: 0.938 AC: 37228 AN: 39678

South Asian (SAS) AF: 0.780 AC: 67147 AN: 86128

European-Finnish (FIN) AF: 0.725 AC: 38659 AN: 53312

Middle Eastern (MID) AF: 0.661 AC: 3812 AN: 5768

European-Non Finnish (NFE) AF: 0.724 AC: 804793 AN: 1111410

Other (OTH) AF: 0.730 AC: 43992 AN: 60304

GnomAD4 genome AF: 0.740 AC: 112530 AN: 152168 Hom.: 42118 Cov.: 33 AF XY: 0.737 AC XY: 54851 AN XY: 74380

African (AFR) AF: 0.817 AC: 33966 AN: 41550

American (AMR) AF: 0.600 AC: 9174 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2354 AN: 3470

East Asian (EAS) AF: 0.923 AC: 4775 AN: 5176

South Asian (SAS) AF: 0.794 AC: 3827 AN: 4822

European-Finnish (FIN) AF: 0.714 AC: 7547 AN: 10574

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48633 AN: 67976

Other (OTH) AF: 0.709 AC: 1495 AN: 2110

Alfa AF: 0.724 Hom.: 116401

Bravo AF: 0.734

Asia WGS AF: 0.868 AC: 3017 AN: 3478

EpiCase AF: 0.710

EpiControl AF: 0.706

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 42 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.37
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs2877561; hg19: chr3-121712051; COSMIC: COSV56552211;