3-66381178-A-G

Position:

• chr3-66381178-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015541.3(LRIG1):​c.2770+301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,048 control chromosomes in the GnomAD database, including 31,054 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 0.63 (31054 hom., cov: 32)
• Consequence: LRIG1 NM_015541.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840

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]

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

LRIG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIG1	NM_015541.3	c.2770+301T>C		intron_variant		ENST00000273261.8	NP_056356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIG1	ENST00000273261.8	c.2770+301T>C		intron_variant		1	NM_015541.3	ENSP00000273261.3

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96343 AN: 151930 Hom.: 30995 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.634 AC: 96464 AN: 152048 Hom.: 31054 Cov.: 32 AF XY: 0.636 AC XY: 47291 AN XY: 74326

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.610

Alfa AF: 0.568 Hom.: 16425

Bravo AF: 0.643

Asia WGS AF: 0.717 AC: 2494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.62

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: rs2242285; hg19: chr3-66431602;