15-100569022-A-G

Position:

• chr15-100569022-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040616.3(LINS1):​c.*216T>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 0.392 in 403,440 control chromosomes in the GnomAD database, including 33,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11460 hom., cov: 26)
  • Exomes 𝑓: 0.40 (22017 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 15-100569022-A-G is Benign according to our data. Variant chr15-100569022-A-G is described in ClinVar as [Benign]. Clinvar id is 1283347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*216T>C		3_prime_UTR_variant	7/7	ENST00000314742.13	NP_001035706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINS1	ENST00000314742.13	c.*216T>C		3_prime_UTR_variant	7/7	5	NM_001040616.3	ENSP00000318423	P1
LINS1	ENST00000560783.1	c.192-3757T>C		intron_variant, NMD_transcript_variant		5		ENSP00000474128

Frequencies

GnomAD3 genomes AF: 0.379 AC: 56751 AN: 149908 Hom.: 11458 Cov.: 26

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.400 AC: 101438 AN: 253418 Hom.: 22017 Cov.: 0 AF XY: 0.398 AC XY: 53578 AN XY: 134590

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.378 AC: 56768 AN: 150022 Hom.: 11460 Cov.: 26 AF XY: 0.375 AC XY: 27365 AN XY: 73070

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.385

Alfa AF: 0.412 Hom.: 1648

Bravo AF: 0.361

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.40

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: rs3751549; hg19: chr15-101109227;