rs11172796

chr12-58885878-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_153377.5(LRIG3):c.1197T>A(p.Arg399=) 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 12-58885878-A-T is Benign according to our data. Variant chr12-58885878-A-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
LRIG3	NM_153377.5	c.1197T>A	p.Arg399=	synonymous_variant	10/19	ENST00000320743.8
LRIG3	NM_001136051.3	c.1017T>A	p.Arg339=	synonymous_variant	10/19
LRIG3	XM_017018790.3	c.1197T>A	p.Arg399=	synonymous_variant	10/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIG3	ENST00000320743.8	c.1197T>A	p.Arg399=	synonymous_variant	10/19	1	NM_153377.5	P1
LRIG3	ENST00000379141.8	c.1017T>A	p.Arg339=	synonymous_variant	10/19	1
LRIG3	ENST00000433272.6	c.1197T>A	p.Arg399=	synonymous_variant, NMD_transcript_variant	10/20	1
LRIG3	ENST00000550304.1			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

GnomAD3 exomes AF: 0.119 AC: 29633 AN: 249248 Hom.: 2370 AF XY: 0.110 AC XY: 14845 AN XY: 134752

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 SAS exome AF: 0.0915

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

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.0600

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.0904

Gnomad4 FIN exome AF: 0.0944

Gnomad4 NFE exome AF: 0.0852

Gnomad4 OTH exome AF: 0.107

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

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0994

Gnomad4 FIN AF: 0.0951

Gnomad4 NFE AF: 0.0888

Gnomad4 OTH AF: 0.144

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11172796; hg19: chr12-59279660; COSMIC: COSV57860970; COSMIC: COSV57860970;