chr15-100569153-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040616.3(LINS1):​c.*85T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 783,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00052 (0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 146680 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.000116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000516 AC: 329 AN: 637232 Hom.: 0 Cov.: 9 AF XY: 0.000496 AC XY: 166 AN XY: 334754

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

African (AFR) AF: 0.000324 AC: 5 AN: 15444

American (AMR) AF: 0.0000437 AC: 1 AN: 22880

Ashkenazi Jewish (ASJ) AF: 0.000245 AC: 4 AN: 16342

East Asian (EAS) AF: 0.0000304 AC: 1 AN: 32852

South Asian (SAS) AF: 0.0000931 AC: 5 AN: 53720

European-Finnish (FIN) AF: 0.0000732 AC: 3 AN: 40966

Middle Eastern (MID) AF: 0.000395 AC: 1 AN: 2534

European-Non Finnish (NFE) AF: 0.000713 AC: 300 AN: 420816

Other (OTH) AF: 0.000284 AC: 9 AN: 31678

⚠️ 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: 0.0000136 AC: 2 AN: 146748 Hom.: 0 Cov.: 27 AF XY: 0.0000282 AC XY: 2 AN XY: 70894

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

African (AFR) AF: 0.00 AC: 0 AN: 39858

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: 0.000213 AC: 1 AN: 4688

European-Finnish (FIN) AF: 0.000116 AC: 1 AN: 8620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67268

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		0.012

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;