Genetic Variant LINS1:c.*110_*115dupTTTTTT (chr15-100569122-C-CAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001040616.3(LINS1):c.*110_*115dupTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LINS1
NM_001040616.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability, autosomal recessive 27
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LINS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3 link	c.110_115dupTTTTTT		3_prime_UTR_variant	Exon 7 of 7	ENST00000314742.13	NP_001035706.2	Q8NG48-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LINS1	ENST00000314742.13 link	c.110_115dupTTTTTT	3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8	Q8NG48-1
LINS1	ENST00000560783.1 link	n.191-3863_191-3858dupTTTTTT	intron_variant	Intron 1 of 3	5		ENSP00000474128.1	S4R3B7
LINS1	ENST00000559169.1 link	n.107_112dupTTTTTT	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

106108

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000458

AC:

AN:

371278

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

196022

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000943

AC:

AN:

10602

American (AMR)

AF:

0.00

AC:

AN:

14714

Ashkenazi Jewish (ASJ)

AF:

0.000186

AC:

AN:

10748

East Asian (EAS)

AF:

0.00

AC:

AN:

25408

South Asian (SAS)

AF:

0.0000534

AC:

AN:

37454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1514

European-Non Finnish (NFE)

AF:

0.0000478

AC:

AN:

230112

Other (OTH)

AF:

0.0000489

AC:

AN:

20432

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.243

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

106108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

48622

African (AFR)

AF:

0.00

AC:

AN:

27544

American (AMR)

AF:

0.00

AC:

AN:

9290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2882

East Asian (EAS)

AF:

0.00

AC:

AN:

2986

South Asian (SAS)

AF:

0.00

AC:

AN:

2972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

55054

Other (OTH)

AF:

0.00

AC:

AN:

1342

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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15-100569122-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over