chr15-100569153-A-C

Variant names:

• chr15-100569153-A-C
• rs28438569
• NM_001040616.3:c.*85T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001040616.3(LINS1):​c.*85T>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 0.00122 in 784,320 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00089 (1 hom., cov: 27)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000893 (131/146748) while in subpopulation NFE AF = 0.00162 (109/67266). AF 95% confidence interval is 0.00137. There are 1 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*85T>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.*85T>G		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3888T>G		intron_variant	Intron 1 of 3	5		ENSP00000474128.1
LINS1	ENST00000559169.1	n.*82T>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000893 AC: 131 AN: 146680 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00149

Gnomad FIN AF: 0.000232

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00130 AC: 828 AN: 637572 Hom.: 3 Cov.: 9 AF XY: 0.00130 AC XY: 436 AN XY: 334924

African (AFR) AF: 0.000388 AC: 6 AN: 15450

American (AMR) AF: 0.0000874 AC: 2 AN: 22882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16350

East Asian (EAS) AF: 0.00 AC: 0 AN: 32856

South Asian (SAS) AF: 0.000856 AC: 46 AN: 53728

European-Finnish (FIN) AF: 0.000122 AC: 5 AN: 40990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2536

European-Non Finnish (NFE) AF: 0.00177 AC: 746 AN: 421082

Other (OTH) AF: 0.000726 AC: 23 AN: 31698

GnomAD4 genome AF: 0.000893 AC: 131 AN: 146748 Hom.: 1 Cov.: 27 AF XY: 0.000832 AC XY: 59 AN XY: 70896

African (AFR) AF: 0.000326 AC: 13 AN: 39860

American (AMR) AF: 0.00 AC: 0 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5012

South Asian (SAS) AF: 0.00149 AC: 7 AN: 4688

European-Finnish (FIN) AF: 0.000232 AC: 2 AN: 8620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00162 AC: 109 AN: 67266

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.000168 Hom.: 691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.38
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism

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: rs28438569; hg19: chr15-101109358;