rs11709533

Variant names:

• chr3-66489204-T-C
• rs11709533
• NM_015541.3:c.218+10986A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015541.3(LRIG1):​c.218+10986A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,094 control chromosomes in the GnomAD database, including 52,032 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 0.77 (52032 hom., cov: 31)
• Consequence: LRIG1 NM_015541.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 6 publications found

Genes affected

LRIG1 (HGNC:17360): (leucine rich repeats and immunoglobulin like domains 1) Predicted to act upstream of or within several processes, including innervation; otolith morphogenesis; and sensory perception of sound. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIG1	NM_015541.3	c.218+10986A>G		intron_variant	Intron 1 of 18	ENST00000273261.8	NP_056356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIG1	ENST00000273261.8	c.218+10986A>G		intron_variant	Intron 1 of 18	1	NM_015541.3	ENSP00000273261.3
LRIG1	ENST00000383703.3	c.218+10986A>G		intron_variant	Intron 1 of 19	1		ENSP00000373208.3
LRIG1	ENST00000475366.5	n.113+8943A>G		intron_variant	Intron 1 of 4	4
LRIG1	ENST00000498287.5	n.171+11889A>G		intron_variant	Intron 1 of 5	4

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117153 AN: 151976 Hom.: 52024 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.801

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.770 AC: 117179 AN: 152094 Hom.: 52032 Cov.: 31 AF XY: 0.772 AC XY: 57439 AN XY: 74382

African (AFR) AF: 0.291 AC: 12061 AN: 41416

American (AMR) AF: 0.855 AC: 13074 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3151 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4377 AN: 5154

South Asian (SAS) AF: 0.961 AC: 4632 AN: 4820

European-Finnish (FIN) AF: 0.937 AC: 9934 AN: 10598

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67081 AN: 68030

Other (OTH) AF: 0.800 AC: 1688 AN: 2110

Alfa AF: 0.913 Hom.: 185206

Bravo AF: 0.741

Asia WGS AF: 0.835 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-0.23
Mutation Taster		=100/0	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: rs11709533; hg19: chr3-66539628;