1-113093538-A-G

Variant names:

• chr1-113093538-A-G
• rs6688685
• NM_014813.3:c.489A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_014813.3(LRIG2):​c.489A>G​(p.Ser163Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00844 in 1,584,488 control chromosomes in the GnomAD database, including 1,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.046 (524 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (482 hom.)
• Consequence: LRIG2 NM_014813.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.330

Genes affected

LRIG2 (HGNC:20889): (leucine rich repeats and immunoglobulin like domains 2) This gene encodes a transmembrane protein containing leucine-rich repeats and immunoglobulin-like domains. The encoded protein promotes epidermal growth factor signalling, resulting in increased proliferation. Its expression in the cytoplasm of glioma cells is correlated with poor survival. Mutations in this gene can cause urofacial syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-113093538-A-G is Benign according to our data. Variant chr1-113093538-A-G is described in ClinVar as [Benign]. Clinvar id is 3344535.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIG2	NM_014813.3	c.489A>G	p.Ser163Ser	synonymous_variant	Exon 4 of 18	ENST00000361127.6	NP_055628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIG2	ENST00000361127.6	c.489A>G	p.Ser163Ser	synonymous_variant	Exon 4 of 18	1	NM_014813.3	ENSP00000355396.4

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6799 AN: 147884 Hom.: 520 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.000534

Gnomad OTH AF: 0.0280

GnomAD3 exomes AF: 0.0118 AC: 2958 AN: 251282 Hom.: 208 AF XY: 0.00845 AC XY: 1148 AN XY: 135854

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.00868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00456 AC: 6550 AN: 1436500 Hom.: 482 Cov.: 31 AF XY: 0.00385 AC XY: 2752 AN XY: 714432

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.00999

Gnomad4 ASJ exome AF: 0.0000793

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000407

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0461 AC: 6826 AN: 147988 Hom.: 524 Cov.: 31 AF XY: 0.0448 AC XY: 3218 AN XY: 71756

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00128

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000534

Gnomad4 OTH AF: 0.0277

Alfa AF: 0.00836 Hom.: 171

Bravo AF: 0.0515

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LRIG2-related disorder Benign:1

Jun 06, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.3
DANN	Benign	0.76

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: rs6688685; hg19: chr1-113636160;