15-100569187-C-T

Variant names:

• chr15-100569187-C-T
• rs79985453
• NM_001040616.3:c.*51G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040616.3(LINS1):​c.*51G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 1,200,226 control chromosomes in the GnomAD database, including 4,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (410 hom., cov: 31)
  • Exomes 𝑓: 0.087 (4365 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-100569187-C-T is Benign according to our data. Variant chr15-100569187-C-T is described in ClinVar as [Benign]. Clinvar id is 1256652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*51G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000314742.13	NP_001035706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINS1	ENST00000314742.13	c.*51G>A		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3922G>A		intron_variant	Intron 1 of 3	5		ENSP00000474128.1
LINS1	ENST00000559169.1	n.*48G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9572 AN: 149058 Hom.: 409 Cov.: 31

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0566

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.0861

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0723

GnomAD2 exomes AF: 0.0627 AC: 14218 AN: 226814 AF XY: 0.0649

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.0477

Gnomad EAS exome AF: 0.000176

Gnomad FIN exome AF: 0.0434

Gnomad NFE exome AF: 0.0959

Gnomad OTH exome AF: 0.0695

GnomAD4 exome AF: 0.0866 AC: 91031 AN: 1051110 Hom.: 4365 Cov.: 15 AF XY: 0.0853 AC XY: 45893 AN XY: 538280

African (AFR) AF: 0.0157 AC: 384 AN: 24508

American (AMR) AF: 0.0470 AC: 1870 AN: 39822

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 1121 AN: 22606

East Asian (EAS) AF: 0.000190 AC: 7 AN: 36820

South Asian (SAS) AF: 0.0434 AC: 3236 AN: 74558

European-Finnish (FIN) AF: 0.0475 AC: 2416 AN: 50878

Middle Eastern (MID) AF: 0.0647 AC: 284 AN: 4388

European-Non Finnish (NFE) AF: 0.104 AC: 78120 AN: 751524

Other (OTH) AF: 0.0781 AC: 3593 AN: 46006

GnomAD4 genome AF: 0.0641 AC: 9564 AN: 149116 Hom.: 410 Cov.: 31 AF XY: 0.0617 AC XY: 4476 AN XY: 72560

African (AFR) AF: 0.0191 AC: 775 AN: 40542

American (AMR) AF: 0.0616 AC: 927 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.0566 AC: 195 AN: 3446

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5086

South Asian (SAS) AF: 0.0394 AC: 185 AN: 4696

European-Finnish (FIN) AF: 0.0451 AC: 432 AN: 9580

Middle Eastern (MID) AF: 0.0750 AC: 21 AN: 280

European-Non Finnish (NFE) AF: 0.101 AC: 6787 AN: 67484

Other (OTH) AF: 0.0716 AC: 147 AN: 2052

Alfa AF: 0.0648 Hom.: 273

Bravo AF: 0.0616

Asia WGS AF: 0.0180 AC: 62 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.26
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79985453; hg19: chr15-101109392;