Genetic Variant NM_001040616.3:c.*51G>T (chr15-100569187-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040616.3(LINS1):c.*51G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 9.5e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LINS1
NM_001040616.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

3 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3 link	c.*51G>T		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.*51G>T	3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8	Q8NG48-1
LINS1	ENST00000560783.1 link	n.191-3922G>T	intron_variant	Intron 1 of 3	5		ENSP00000474128.1	S4R3B7
LINS1	ENST00000559169.1 link	n.*48G>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149096

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

AF:

9.50e-7

AC:

AN:

1052248

Hom.:

Cov.:

AF XY:

0.00000186

AC XY:

AN XY:

538828

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

24510

American (AMR)

AF:

0.00

AC:

AN:

39848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22620

East Asian (EAS)

AF:

0.00

AC:

AN:

36820

South Asian (SAS)

AF:

0.00

AC:

AN:

74582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4394

European-Non Finnish (NFE)

AF:

0.00000133

AC:

AN:

752546

Other (OTH)

AF:

0.00

AC:

AN:

46032

⚠️ 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: 0.225

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;AS_VQSR

AF:

0.00

AC:

AN:

149096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72514

African (AFR)

AF:

0.00

AC:

AN:

40474

American (AMR)

AF:

0.00

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67508

Other (OTH)

AF:

0.00

AC:

AN:

2036

Alfa

AF:

0.00

Hom.:

273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.49

(source)

DANN

Benign

0.30

PhyloP100

-1.4

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

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NM_001040616.3:c.*51G>T

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