chr3-122006995-T-C

Variant names:

• chr3-122006995-T-C
• rs146402126
• NM_001199799.2:c.225A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001199799.2(ILDR1):​c.225A>G​(p.Ser75Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,612,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: ILDR1 NM_001199799.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.639
• 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: 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 3-122006995-T-C is Benign according to our data. Variant chr3-122006995-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.639 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00092 (140/152132) while in subpopulation AFR AF = 0.00313 (130/41484). AF 95% confidence interval is 0.0027. There are 0 homozygotes in GnomAd4. There are 64 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.225A>G	p.Ser75Ser	synonymous	Exon 2 of 8	NP_001186728.1	Q86SU0-1
	ILDR1	NM_175924.4		c.225A>G	p.Ser75Ser	synonymous	Exon 2 of 7	NP_787120.1	Q86SU0-2
	ILDR1	NM_001199800.2		c.225A>G	p.Ser75Ser	synonymous	Exon 2 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.225A>G	p.Ser75Ser	synonymous	Exon 2 of 8	ENSP00000345667.5	Q86SU0-1
	ILDR1	ENST00000273691.7	TSL:1	c.225A>G	p.Ser75Ser	synonymous	Exon 2 of 7	ENSP00000273691.3	Q86SU0-2
	ILDR1	ENST00000393631.5	TSL:1	c.225A>G	p.Ser75Ser	synonymous	Exon 2 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes AF: 0.000914 AC: 139 AN: 152014 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000284 AC: 71 AN: 250398 AF XY: 0.000170

Gnomad AFR exome AF: 0.00390

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.0000993 AC: 145 AN: 1460148 Hom.: 0 Cov.: 31 AF XY: 0.0000922 AC XY: 67 AN XY: 726330

African (AFR) AF: 0.00341 AC: 114 AN: 33434

American (AMR) AF: 0.0000224 AC: 1 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000216 AC: 1 AN: 4630

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111814

Other (OTH) AF: 0.000282 AC: 17 AN: 60270

GnomAD4 genome AF: 0.000920 AC: 140 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.000860 AC XY: 64 AN XY: 74380

African (AFR) AF: 0.00313 AC: 130 AN: 41484

American (AMR) AF: 0.000589 AC: 9 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000847 Hom.: 0

Bravo AF: 0.00107

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.5
DANN	Benign	0.54
PhyloP100		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146402126; hg19: chr3-121725842;