chr3-121993587-A-G

Variant names:

• chr3-121993587-A-G
• rs35661993
• NM_001199799.2:c.1162T>C

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.1162T>C​(p.Trp388Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,614,156 control chromosomes in the GnomAD database, including 117 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (51 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.273
• Publications: 8 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, PanelApp Australia, 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=0.0029866695).
• BP6: Variant 3-121993587-A-G is Benign according to our data. Variant chr3-121993587-A-G is described in ClinVar as Benign. ClinVar VariationId is 44136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 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.1162T>C	p.Trp388Arg	missense	Exon 7 of 8	NP_001186728.1	Q86SU0-1
	ILDR1	NM_175924.4		c.1030T>C	p.Trp344Arg	missense	Exon 6 of 7	NP_787120.1	Q86SU0-2
	ILDR1	NM_001199800.2		c.895T>C	p.Trp299Arg	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.1162T>C	p.Trp388Arg	missense	Exon 7 of 8	ENSP00000345667.5	Q86SU0-1
	ILDR1	ENST00000273691.7	TSL:1	c.1030T>C	p.Trp344Arg	missense	Exon 6 of 7	ENSP00000273691.3	Q86SU0-2
	ILDR1	ENST00000393631.5	TSL:1	c.895T>C	p.Trp299Arg	missense	Exon 5 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2290 AN: 152144 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00397 AC: 998 AN: 251484 AF XY: 0.00294

Gnomad AFR exome AF: 0.0504

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00186 AC: 2725 AN: 1461894 Hom.: 51 Cov.: 40 AF XY: 0.00163 AC XY: 1187 AN XY: 727248

African (AFR) AF: 0.0530 AC: 1776 AN: 33480

American (AMR) AF: 0.00358 AC: 160 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000394 AC: 34 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.000344 AC: 383 AN: 1112012

Other (OTH) AF: 0.00525 AC: 317 AN: 60396

GnomAD4 genome AF: 0.0151 AC: 2304 AN: 152262 Hom.: 66 Cov.: 32 AF XY: 0.0152 AC XY: 1128 AN XY: 74448

African (AFR) AF: 0.0514 AC: 2134 AN: 41540

American (AMR) AF: 0.00804 AC: 123 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68018

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00545 Hom.: 28

Bravo AF: 0.0173

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0468 AC: 206

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00474 AC: 576

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 42 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.27
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Benign	0.94	T
Polyphen		0.99	D
Vest4		0.16
MutPred		0.22		Gain of phosphorylation at S387 (P = 0.0767)
MVP		0.74
MPC		0.060
ClinPred		0.0099	T
GERP RS		0.035
Varity_R		0.14
gMVP		0.19
Mutation Taster		=99/1	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: rs35661993; hg19: chr3-121712434;