rs1403625

Variant names:

• chr3-66500332-G-C
• rs1403625
• NM_015541.3:c.76C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-66500332-G-C
• chr3-66500332-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015541.3(LRIG1):​c.76C>G​(p.Leu26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,494,546 control chromosomes in the GnomAD database, including 679,457 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (51660 hom., cov: 31)
  • Exomes 𝑓: 0.96 (627797 hom.)
• Consequence: LRIG1 NM_015541.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.33
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.704122E-7).
• BP6: Variant 3-66500332-G-C is Benign according to our data. Variant chr3-66500332-G-C is described in ClinVar as Benign. ClinVar VariationId is 403057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIG1	NM_015541.3	MANE Select	c.76C>G	p.Leu26Val	missense	Exon 1 of 19	NP_056356.2	Q96JA1-1
	LRIG1	NM_001377344.1		c.76C>G	p.Leu26Val	missense	Exon 1 of 18	NP_001364273.1
	LRIG1	NM_001377345.1		c.-563+761C>G		intron	N/A	NP_001364274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIG1	ENST00000273261.8	TSL:1 MANE Select	c.76C>G	p.Leu26Val	missense	Exon 1 of 19	ENSP00000273261.3	Q96JA1-1
	LRIG1	ENST00000383703.3	TSL:1	c.76C>G	p.Leu26Val	missense	Exon 1 of 20	ENSP00000373208.3	Q96JA1-2
	LRIG1	ENST00000895940.1		c.76C>G	p.Leu26Val	missense	Exon 1 of 20	ENSP00000565999.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116518 AN: 151252 Hom.: 51655 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.920

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.804

GnomAD2 exomes AF: 0.920 AC: 105493 AN: 114698 AF XY: 0.930

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.877

Gnomad ASJ exome AF: 0.910

Gnomad EAS exome AF: 0.807

Gnomad FIN exome AF: 0.929

Gnomad NFE exome AF: 0.985

Gnomad OTH exome AF: 0.921

GnomAD4 exome AF: 0.961 AC: 1290177 AN: 1343186 Hom.: 627797 Cov.: 50 AF XY: 0.963 AC XY: 639956 AN XY: 664780

African (AFR) AF: 0.268 AC: 7533 AN: 28158

American (AMR) AF: 0.878 AC: 23869 AN: 27178

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 20850 AN: 22782

East Asian (EAS) AF: 0.832 AC: 26571 AN: 31942

South Asian (SAS) AF: 0.961 AC: 71239 AN: 74140

European-Finnish (FIN) AF: 0.943 AC: 35076 AN: 37180

Middle Eastern (MID) AF: 0.927 AC: 4401 AN: 4746

European-Non Finnish (NFE) AF: 0.989 AC: 1050057 AN: 1061600

Other (OTH) AF: 0.912 AC: 50581 AN: 55460

GnomAD4 genome AF: 0.770 AC: 116535 AN: 151360 Hom.: 51660 Cov.: 31 AF XY: 0.772 AC XY: 57085 AN XY: 73970

African (AFR) AF: 0.294 AC: 12150 AN: 41326

American (AMR) AF: 0.863 AC: 13125 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3144 AN: 3464

East Asian (EAS) AF: 0.809 AC: 4044 AN: 4996

South Asian (SAS) AF: 0.957 AC: 4618 AN: 4828

European-Finnish (FIN) AF: 0.936 AC: 9824 AN: 10494

Middle Eastern (MID) AF: 0.918 AC: 268 AN: 292

European-Non Finnish (NFE) AF: 0.986 AC: 66759 AN: 67728

Other (OTH) AF: 0.803 AC: 1692 AN: 2108

Alfa AF: 0.796 Hom.: 3308

Bravo AF: 0.741

ESP6500AA AF: 0.484 AC: 1298

ESP6500EA AF: 0.983 AC: 5191

ExAC AF: 0.883 AC: 85766

Asia WGS AF: 0.820 AC: 2812 AN: 3430

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	LRIG1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.60	D
MetaRNN	Benign	8.7e-7	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.068
Sift	Benign	0.35	T
Sift4G	Benign	0.25	T
Polyphen		0.48	P
Vest4		0.19
MPC		0.16
ClinPred		0.0070	T
GERP RS		2.9
Varity_R		0.057
gMVP		0.45
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1403625; hg19: chr3-66550756; COSMIC: COSV56236825; COSMIC: COSV56236825;