15-100569122-C-CA

Variant names:

• chr15-100569122-C-CA
• rs56225071
• NM_001040616.3:c.*115dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001040616.3(LINS1):​c.*115dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (9137 hom., cov: 0)
  • Exomes 𝑓: 0.29 (252 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.597
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 15-100569122-C-CA is Benign according to our data. Variant chr15-100569122-C-CA is described in ClinVar as [Benign]. Clinvar id is 1248118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*115dupT		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.*115dupT		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3858dupT		intron_variant	Intron 1 of 3	5		ENSP00000474128.1
LINS1	ENST00000559169.1	n.*112dupT		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 42290 AN: 106008 Hom.: 9136 Cov.: 0

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.290 AC: 106262 AN: 366628 Hom.: 252 Cov.: 5 AF XY: 0.291 AC XY: 56271 AN XY: 193506

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.258 AC: 2687 AN: 10422

American (AMR) AF: 0.320 AC: 4651 AN: 14522

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 2835 AN: 10638

East Asian (EAS) AF: 0.186 AC: 4652 AN: 25036

South Asian (SAS) AF: 0.301 AC: 11091 AN: 36840

European-Finnish (FIN) AF: 0.304 AC: 6102 AN: 20102

Middle Eastern (MID) AF: 0.277 AC: 411 AN: 1486

European-Non Finnish (NFE) AF: 0.299 AC: 68039 AN: 227372

Other (OTH) AF: 0.287 AC: 5794 AN: 20210

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.399 AC: 42297 AN: 105994 Hom.: 9137 Cov.: 0 AF XY: 0.398 AC XY: 19336 AN XY: 48582

African (AFR) AF: 0.345 AC: 9489 AN: 27526

American (AMR) AF: 0.494 AC: 4595 AN: 9294

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1006 AN: 2870

East Asian (EAS) AF: 0.169 AC: 499 AN: 2954

South Asian (SAS) AF: 0.477 AC: 1408 AN: 2952

European-Finnish (FIN) AF: 0.480 AC: 1453 AN: 3026

Middle Eastern (MID) AF: 0.401 AC: 77 AN: 192

European-Non Finnish (NFE) AF: 0.417 AC: 22929 AN: 55032

Other (OTH) AF: 0.398 AC: 537 AN: 1348

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60
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: rs56225071; hg19: chr15-101109327;