rs145145735

Positions:

chr15-100574155-G-A

Variant summary

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

The NM_001352507.2(LINS1):c.-30C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000765 in 1,613,688 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 3 hom. )

Consequence

LINS1
NM_001352507.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.45

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=0.0037718415).

BP6

Variant 15-100574155-G-A is Benign according to our data. Variant chr15-100574155-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00378 (575/152226) while in subpopulation AFR AF= 0.0134 (556/41546). AF 95% confidence interval is 0.0125. There are 1 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINS1	NM_001040616.3 linkuse as main transcript	c.718C>T	p.Arg240Trp	missense_variant	5/7	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.718C>T	p.Arg240Trp	missense_variant	5/7	5	NM_001040616.3	ENSP00000318423.8	Q8NG48-1
LINS1	ENST00000561308.5 linkuse as main transcript	c.718C>T	p.Arg240Trp	missense_variant	5/5	1		ENSP00000454200.1	Q8NG48-2
LINS1	ENST00000560133.5 linkuse as main transcript	c.361C>T	p.Arg121Trp	missense_variant	5/5	2		ENSP00000454929.1	H3BNM9
LINS1	ENST00000559149.5 linkuse as main transcript	n.875C>T		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

575

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00116

AC:

289

AN:

250020

Hom.:

AF XY:

0.000796

AC XY:

108

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.000724

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000452

AC:

660

AN:

1461462

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

288

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00378

AC:

575

AN:

152226

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000731

Hom.:

Bravo

AF:

0.00458

ESP6500AA

AF:

0.0153

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00147

AC:

179

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	LINS1: BP4, BS1 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 20, 2015

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2019

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

0.093

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0026

T;.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.69

N;N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.3

N;N;D

REVEL

Benign

0.14

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.036

D;D;D

Polyphen

0.85

P;P;.

Vest4

0.18

MVP

0.77

MPC

0.081

ClinPred

0.015

GERP RS

5.3

Varity_R

0.11

gMVP

0.13

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