15-100569038-T-C

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.*200A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 148,678 control chromosomes in the GnomAD database, including 11,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11398 hom., cov: 25)
  • Exomes 𝑓: 0.39 (24147 hom.)
  • Failed GnomAD Quality Control
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.877

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=-1.02).
• BP6: Variant 15-100569038-T-C is Benign according to our data. Variant chr15-100569038-T-C is described in ClinVar as [Benign]. Clinvar id is 1181619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINS1	NM_001040616.3	c.*200A>G		3_prime_UTR_variant	7/7	ENST00000314742.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINS1	ENST00000314742.13	c.*200A>G		3_prime_UTR_variant	7/7	5	NM_001040616.3	P1
LINS1	ENST00000560783.1	c.192-3773A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.380 AC: 56437 AN: 148574 Hom.: 11396 Cov.: 25

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.385

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.394 AC: 111506 AN: 282862 Hom.: 24147 Cov.: 0 AF XY: 0.393 AC XY: 58905 AN XY: 149952

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.380 AC: 56452 AN: 148678 Hom.: 11398 Cov.: 25 AF XY: 0.376 AC XY: 27173 AN XY: 72266

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.384

Alfa AF: 0.403 Hom.: 1562

Bravo AF: 0.361

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 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.8
Dann	Benign	0.065

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: rs3751550; hg19: chr15-101109243;