chr3-66429063-G-A

Variant names:

• chr3-66429063-G-A
• rs13078828
• NM_015541.3:c.366-11797C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_015541.3(LRIG1):​c.366-11797C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 152,326 control chromosomes in the GnomAD database, including 87 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 0.026 (87 hom., cov: 33)
• Consequence: LRIG1 NM_015541.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 7 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=-0.39).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0261 (3977/152326) while in subpopulation NFE AF = 0.0424 (2884/68022). AF 95% confidence interval is 0.0411. There are 87 homozygotes in GnomAd4. There are 1882 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3977 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIG1	NM_015541.3	c.366-11797C>T		intron_variant	Intron 3 of 18	ENST00000273261.8	NP_056356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIG1	ENST00000273261.8	c.366-11797C>T		intron_variant	Intron 3 of 18	1	NM_015541.3	ENSP00000273261.3
LRIG1	ENST00000383703.3	c.366-11797C>T		intron_variant	Intron 3 of 19	1		ENSP00000373208.3
LRIG1	ENST00000475366.5	n.261-11797C>T		intron_variant	Intron 3 of 4	4
LRIG1	ENST00000498287.5	n.319-11797C>T		intron_variant	Intron 3 of 5	4

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3981 AN: 152208 Hom.: 88 Cov.: 33

Gnomad AFR AF: 0.00784

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0261 AC: 3977 AN: 152326 Hom.: 87 Cov.: 33 AF XY: 0.0253 AC XY: 1882 AN XY: 74494

African (AFR) AF: 0.00782 AC: 325 AN: 41574

American (AMR) AF: 0.0144 AC: 220 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0424 AC: 2884 AN: 68022

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0371 Hom.: 354

Bravo AF: 0.0232

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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: rs13078828; hg19: chr3-66479487; COSMIC: COSV56241203;