3-66380737-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_015541.3(LRIG1):​c.2895G>A​(p.Pro965Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,614,208 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00050 ( 9 hom. )

Consequence

LRIG1
NM_015541.3 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.361
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 3-66380737-C-T is Benign according to our data. Variant chr3-66380737-C-T is described in ClinVar as [Benign]. Clinvar id is 3043420.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.361 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000503 (736/1461880) while in subpopulation EAS AF= 0.0161 (641/39700). AF 95% confidence interval is 0.0151. There are 9 homozygotes in gnomad4_exome. There are 373 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 89 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRIG1NM_015541.3 linkc.2895G>A p.Pro965Pro synonymous_variant Exon 18 of 19 ENST00000273261.8 NP_056356.2 Q96JA1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRIG1ENST00000273261.8 linkc.2895G>A p.Pro965Pro synonymous_variant Exon 18 of 19 1 NM_015541.3 ENSP00000273261.3 Q96JA1-1

Frequencies

GnomAD3 genomes
AF:
0.000585
AC:
89
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0155
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000947
AC:
238
AN:
251390
Hom.:
3
AF XY:
0.000876
AC XY:
119
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.0119
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000651
GnomAD4 exome
AF:
0.000503
AC:
736
AN:
1461880
Hom.:
9
Cov.:
33
AF XY:
0.000513
AC XY:
373
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.0161
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.000381
GnomAD4 genome
AF:
0.000584
AC:
89
AN:
152328
Hom.:
0
Cov.:
33
AF XY:
0.000725
AC XY:
54
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0155
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000134
Hom.:
0
Bravo
AF:
0.000695
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

LRIG1-related disorder Benign:1
Aug 09, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
7.6
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2279288; hg19: chr3-66431161; API