15-100569038-T-C

Variant names:

• chr15-100569038-T-C
• rs3751550
• NM_001040616.3:c.*200A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.877
• Publications: 1 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 -20 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_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 rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*200A>G		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.*200A>G		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3773A>G		intron_variant	Intron 1 of 3	5		ENSP00000474128.1
LINS1	ENST00000559169.1	n.*197A>G		downstream_gene_variant		2

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

African (AFR) AF: 0.257 AC: 2240 AN: 8724

American (AMR) AF: 0.221 AC: 2510 AN: 11366

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 3131 AN: 8994

East Asian (EAS) AF: 0.229 AC: 4389 AN: 19196

South Asian (SAS) AF: 0.368 AC: 11844 AN: 32146

European-Finnish (FIN) AF: 0.366 AC: 4916 AN: 13428

Middle Eastern (MID) AF: 0.358 AC: 457 AN: 1278

European-Non Finnish (NFE) AF: 0.443 AC: 75850 AN: 171364

Other (OTH) AF: 0.377 AC: 6169 AN: 16366

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

African (AFR) AF: 0.276 AC: 11114 AN: 40270

American (AMR) AF: 0.278 AC: 4113 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1382 AN: 3436

East Asian (EAS) AF: 0.238 AC: 1189 AN: 4998

South Asian (SAS) AF: 0.368 AC: 1732 AN: 4704

European-Finnish (FIN) AF: 0.407 AC: 4013 AN: 9852

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.469 AC: 31611 AN: 67374

Other (OTH) AF: 0.384 AC: 792 AN: 2062

Alfa AF: 0.403 Hom.: 1562

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

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.065
PhyloP100		-0.88
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: rs3751550; hg19: chr15-101109243;