15-100569187-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -1.40

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
LINS1	NM_001040616.3	c.*51G>A		3_prime_UTR_variant	7/7	ENST00000314742.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINS1	ENST00000314742.13	c.*51G>A		3_prime_UTR_variant	7/7	5	NM_001040616.3	P1
LINS1	ENST00000560783.1	c.192-3922G>A		intron_variant, NMD_transcript_variant		5
LINS1	ENST00000559169.1			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

GnomAD3 exomes AF: 0.0627 AC: 14218 AN: 226814 Hom.: 603 AF XY: 0.0649 AC XY: 8044 AN XY: 123904

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 SAS exome AF: 0.0427

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

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.0470

Gnomad4 ASJ exome AF: 0.0496

Gnomad4 EAS exome AF: 0.000190

Gnomad4 SAS exome AF: 0.0434

Gnomad4 FIN exome AF: 0.0475

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0781

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

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.0566

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0451

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0727 Hom.: 95

Bravo AF: 0.0616

Asia WGS AF: 0.0180 AC: 62 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.63
Dann	Benign	0.26

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

Other links and lift over

dbSNP: rs79985453; hg19: chr15-101109392;