rs11172796

Variant names:

• chr12-58885878-A-T
• rs11172796
• NM_153377.5:c.1197T>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153377.5(LRIG3):​c.1197T>A​(p.Arg399Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,585,378 control chromosomes in the GnomAD database, including 10,980 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2987 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7993 hom.)
• Consequence: LRIG3 NM_153377.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 15 publications found

Genes affected

LRIG3 (HGNC:30991): (leucine rich repeats and immunoglobulin like domains 3) Predicted to act upstream of or within otolith morphogenesis. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.013 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIG3	NM_153377.5	c.1197T>A	p.Arg399Arg	synonymous_variant	Exon 10 of 19	ENST00000320743.8	NP_700356.2
LRIG3	NM_001136051.3	c.1017T>A	p.Arg339Arg	synonymous_variant	Exon 10 of 19		NP_001129523.1
LRIG3	XM_017018790.3	c.1197T>A	p.Arg399Arg	synonymous_variant	Exon 10 of 14		XP_016874279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIG3	ENST00000320743.8	c.1197T>A	p.Arg399Arg	synonymous_variant	Exon 10 of 19	1	NM_153377.5	ENSP00000326759.3
LRIG3	ENST00000379141.8	c.1017T>A	p.Arg339Arg	synonymous_variant	Exon 10 of 19	1		ENSP00000368436.4
LRIG3	ENST00000433272.6	n.1197T>A		non_coding_transcript_exon_variant	Exon 10 of 20	1		ENSP00000413143.2
LRIG3	ENST00000550304.1	n.*2T>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25111 AN: 152010 Hom.: 2960 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.119 AC: 29633 AN: 249248 AF XY: 0.110

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.0602

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.0977

Gnomad NFE exome AF: 0.0861

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0959 AC: 137499 AN: 1433250 Hom.: 7993 Cov.: 29 AF XY: 0.0946 AC XY: 67467 AN XY: 712984

African (AFR) AF: 0.339 AC: 11037 AN: 32528

American (AMR) AF: 0.174 AC: 7602 AN: 43680

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 1515 AN: 25246

East Asian (EAS) AF: 0.129 AC: 4930 AN: 38324

South Asian (SAS) AF: 0.0904 AC: 7616 AN: 84242

European-Finnish (FIN) AF: 0.0944 AC: 4815 AN: 51000

Middle Eastern (MID) AF: 0.0834 AC: 471 AN: 5646

European-Non Finnish (NFE) AF: 0.0852 AC: 93260 AN: 1094002

Other (OTH) AF: 0.107 AC: 6253 AN: 58582

GnomAD4 genome AF: 0.166 AC: 25190 AN: 152128 Hom.: 2987 Cov.: 32 AF XY: 0.164 AC XY: 12178 AN XY: 74384

African (AFR) AF: 0.332 AC: 13768 AN: 41460

American (AMR) AF: 0.167 AC: 2555 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.145 AC: 747 AN: 5168

South Asian (SAS) AF: 0.0994 AC: 480 AN: 4828

European-Finnish (FIN) AF: 0.0951 AC: 1008 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0888 AC: 6038 AN: 68004

Other (OTH) AF: 0.144 AC: 305 AN: 2112

Alfa AF: 0.105 Hom.: 396

Bravo AF: 0.175

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		0.013
Mutation Taster		=99/1	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: rs11172796; hg19: chr12-59279660; COSMIC: COSV57860970; COSMIC: COSV57860970;