chr3-66475539-T-C

Variant names:

• chr3-66475539-T-C
• rs3845905
• NM_015541.3:c.219-13030A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015541.3(LRIG1):​c.219-13030A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,088 control chromosomes in the GnomAD database, including 52,399 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 0.80 (52399 hom., cov: 32)
• Consequence: LRIG1 NM_015541.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 12 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015541.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIG1	NM_015541.3	MANE Select	c.219-13030A>G		intron	N/A	NP_056356.2
	LRIG1	NM_001377344.1		c.219-13030A>G		intron	N/A	NP_001364273.1
	LRIG1	NM_001377345.1		c.-562-13030A>G		intron	N/A	NP_001364274.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIG1	ENST00000273261.8	TSL:1 MANE Select	c.219-13030A>G		intron	N/A	ENSP00000273261.3
	LRIG1	ENST00000383703.3	TSL:1	c.219-13030A>G		intron	N/A	ENSP00000373208.3
	LRIG1	ENST00000475366.5	TSL:4	n.114-13030A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121784 AN: 151970 Hom.: 52408 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.801 AC: 121794 AN: 152088 Hom.: 52399 Cov.: 32 AF XY: 0.801 AC XY: 59566 AN XY: 74356

African (AFR) AF: 0.468 AC: 19348 AN: 41386

American (AMR) AF: 0.767 AC: 11730 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4432 AN: 5170

South Asian (SAS) AF: 0.953 AC: 4595 AN: 4820

European-Finnish (FIN) AF: 0.948 AC: 10050 AN: 10606

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65627 AN: 68032

Other (OTH) AF: 0.805 AC: 1696 AN: 2106

Alfa AF: 0.906 Hom.: 109582

Bravo AF: 0.768

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		-0.19
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: rs3845905; hg19: chr3-66525963;