3-66500332-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015541.3(LRIG1):​c.76C>A​(p.Leu26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,343,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: LRIG1 NM_015541.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16857654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIG1	NM_015541.3	c.76C>A	p.Leu26Ile	missense_variant	Exon 1 of 19	ENST00000273261.8	NP_056356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIG1	ENST00000273261.8	c.76C>A	p.Leu26Ile	missense_variant	Exon 1 of 19	1	NM_015541.3	ENSP00000273261.3
LRIG1	ENST00000383703.3	c.76C>A	p.Leu26Ile	missense_variant	Exon 1 of 20	1		ENSP00000373208.3
LRIG1	ENST00000498287.5	n.171+761C>A		intron_variant	Intron 1 of 5	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1343772 Hom.: 0 Cov.: 50 AF XY: 0.00000150 AC XY: 1 AN XY: 665088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.59	D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.088
Sift	Benign	0.12	T;T
Sift4G	Benign	0.067	T;T
Polyphen		0.32	B;P
Vest4		0.28
MutPred		0.45		Loss of disorder (P = 0.0433);Loss of disorder (P = 0.0433);
MVP		0.25
MPC		0.23
ClinPred		0.24	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.34

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: rs1403625; hg19: chr3-66550756;