chr3-66395177-A-G

Variant names:

• chr3-66395177-A-G
• rs9827908
• NM_015541.3:c.1305-974T>C

Variant summary

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

The NM_015541.3(LRIG1):​c.1305-974T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 152,198 control chromosomes in the GnomAD database, including 609 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 0.049 (609 hom., cov: 33)
• Consequence: LRIG1 NM_015541.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.49
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 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.1305-974T>C		intron	N/A	NP_056356.2
	LRIG1	NM_001377344.1		c.1230-974T>C		intron	N/A	NP_001364273.1
	LRIG1	NM_001377345.1		c.525-974T>C		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.1305-974T>C		intron	N/A	ENSP00000273261.3
	LRIG1	ENST00000383703.3	TSL:1	c.1377-974T>C		intron	N/A	ENSP00000373208.3
	LRIG1	ENST00000495037.1	TSL:2	n.321-974T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 7479 AN: 152080 Hom.: 605 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0340

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

GnomAD4 genome AF: 0.0493 AC: 7509 AN: 152198 Hom.: 609 Cov.: 33 AF XY: 0.0475 AC XY: 3533 AN XY: 74420

African (AFR) AF: 0.172 AC: 7128 AN: 41474

American (AMR) AF: 0.0169 AC: 259 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68020

Other (OTH) AF: 0.0336 AC: 71 AN: 2112

Alfa AF: 0.0152 Hom.: 202

Bravo AF: 0.0564

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.58
PhyloP100		-4.5
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: rs9827908; hg19: chr3-66445601;