15-100569153-A-G

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.*85T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 781,654 control chromosomes in the GnomAD database, including 69,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11161 hom., cov: 27)
  • Exomes 𝑓: 0.42 (57973 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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=-0.94).
• BP6: Variant 15-100569153-A-G is Benign according to our data. Variant chr15-100569153-A-G is described in ClinVar as [Benign]. Clinvar id is 1247599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINS1	NM_001040616.3	c.*85T>C		3_prime_UTR_variant	7/7	ENST00000314742.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINS1	ENST00000314742.13	c.*85T>C		3_prime_UTR_variant	7/7	5	NM_001040616.3	P1
LINS1	ENST00000560783.1	c.192-3888T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.376 AC: 54984 AN: 146412 Hom.: 11163 Cov.: 27

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.424 AC: 269236 AN: 635174 Hom.: 57973 Cov.: 9 AF XY: 0.424 AC XY: 141495 AN XY: 333654

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.375 AC: 54984 AN: 146480 Hom.: 11161 Cov.: 27 AF XY: 0.370 AC XY: 26145 AN XY: 70750

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.382

Alfa AF: 0.267 Hom.: 664

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	-0.94
Cadd	Benign	3.1
Dann	Benign	0.31

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: rs28438569; hg19: chr15-101109358;