chr15-100580791-C-T

Position:

chr15-100580791-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001040616.3(LINS1):c.52G>A(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,610,368 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

LINS1
NM_001040616.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

LINS1 (HGNC:30922): (lines homolog 1) The Drosophila segment polarity gene lin encodes a protein, lines, which plays important roles in development of the epidermis and hindgut. This gene encodes a protein containing a lines-like domain. This gene is located on chromosome 15 and clustered with the gene encoding ankyrin repeat and SOCS box-containing protein 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

LINS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067200065).

BP6

Variant 15-100580791-C-T is Benign according to our data. Variant chr15-100580791-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 520599.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.002 (305/152252) while in subpopulation AFR AF= 0.00693 (288/41556). AF 95% confidence interval is 0.00627. There are 1 homozygotes in gnomad4. There are 139 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINS1	NM_001040616.3 linkuse as main transcript	c.52G>A	p.Gly18Arg	missense_variant	2/7	ENST00000314742.13	NP_001035706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINS1	ENST00000314742.13 linkuse as main transcript	c.52G>A	p.Gly18Arg	missense_variant	2/7	5	NM_001040616.3	ENSP00000318423	P1	Q8NG48-1

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

305

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00695

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000558

AC:

139

AN:

248902

Hom.:

AF XY:

0.000342

AC XY:

AN XY:

134596

show subpopulations

Gnomad AFR exome

AF:

0.00686

Gnomad AMR exome

AF:

0.000676

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.000215

AC:

314

AN:

1458116

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

724764

show subpopulations

Gnomad4 AFR exome

AF:

0.00674

Gnomad4 AMR exome

AF:

0.000767

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000747

GnomAD4 genome

AF:

0.00200

AC:

305

AN:

152252

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00693

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.00232

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000692

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 24, 2018

The p.G18R variant (also known as c.52G>A), located in coding exon 1 of the LINS gene, results from a G to A substitution at nucleotide position 52. The glycine at codon 18 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

LINS1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2019

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.;.;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.86

D;D;D;D;D;D

MetaRNN

Benign

0.0067

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;M;.;.;.;.

MutationTaster

Benign

0.94

D;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.8

N;D;D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.011

D;D;D;D;D;D

Sift4G

Uncertain

0.015

D;D;.;.;D;D

Polyphen

1.0

D;P;.;.;.;.

Vest4

0.66

MutPred

0.49

Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);

MVP

0.25

MPC

0.18

ClinPred

0.027

GERP RS

3.8

Varity_R

0.077

gMVP

0.52

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over