chr15-100569699-T-C

Position:

chr15-100569699-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001040616.3(LINS1):c.1813A>G(p.Met605Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,613,844 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 13 hom. )

Consequence

LINS1
NM_001040616.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.04

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:

LINS1 (HGNC:):

LINS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044367015).

BP6

Variant 15-100569699-T-C is Benign according to our data. Variant chr15-100569699-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 211382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-100569699-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00249 (379/152234) while in subpopulation NFE AF= 0.00425 (289/68018). AF 95% confidence interval is 0.00385. There are 2 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINS1	NM_001040616.3 linkuse as main transcript	c.1813A>G	p.Met605Val	missense_variant	7/7	ENST00000314742.13	NP_001035706.2	Q8NG48-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LINS1	ENST00000314742.13 linkuse as main transcript	c.1813A>G	p.Met605Val	missense_variant	7/7	5	NM_001040616.3	ENSP00000318423.8	Q8NG48-1
LINS1	ENST00000559169.1 linkuse as main transcript	n.2088A>G		non_coding_transcript_exon_variant	2/2	2
LINS1	ENST00000560783.1 linkuse as main transcript	n.190+3952A>G		intron_variant		5		ENSP00000474128.1	S4R3B7

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

379

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00425

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00273

AC:

686

AN:

251096

Hom.:

AF XY:

0.00299

AC XY:

406

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.000598

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00494

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00352

AC:

5142

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

2550

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.00427

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00249

AC:

379

AN:

152234

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00425

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00370

Hom.:

Bravo

AF:

0.00244

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00325

AC:

394

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	LINS1: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Nov 07, 2016	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jan 19, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Jun 17, 2015	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2018

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.2

DANN

Benign

0.38

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.44

M_CAP

Benign

0.0079

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.73

REVEL

Benign

0.038

Sift

Benign

0.28

Sift4G

Benign

0.60

Polyphen

0.0060

Vest4

0.11

MVP

0.15

MPC

0.024

ClinPred

0.0025

GERP RS

3.8

Varity_R

0.11

gMVP

0.21

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