15-100569153-A-G

Variant names:

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

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.*85T>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 0.415 in 781,654 control chromosomes in the GnomAD database, including 69,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11161 hom., cov: 27)
  • Exomes 𝑓: 0.42 (57973 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.94).
• BP6: Variant 15-100569153-A-G is Benign according to our data. Variant chr15-100569153-A-G is described in ClinVar as Benign. ClinVar VariationId is 1247599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINS1	NM_001040616.3	MANE Select	c.*85T>C		3_prime_UTR	Exon 7 of 7	NP_001035706.2	Q8NG48-1
	LINS1	NM_001352508.2		c.*85T>C		3_prime_UTR	Exon 7 of 7	NP_001339437.1
	LINS1	NM_001352507.2		c.*85T>C		3_prime_UTR	Exon 8 of 8	NP_001339436.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINS1	ENST00000314742.13	TSL:5 MANE Select	c.*85T>C		3_prime_UTR	Exon 7 of 7	ENSP00000318423.8	Q8NG48-1
	LINS1	ENST00000869606.1		c.*85T>C		3_prime_UTR	Exon 7 of 7	ENSP00000539665.1
	LINS1	ENST00000869607.1		c.*85T>C		3_prime_UTR	Exon 7 of 7	ENSP00000539666.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 54984 AN: 146412 Hom.: 11163 Cov.: 27

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.424 AC: 269236 AN: 635174 Hom.: 57973 Cov.: 9 AF XY: 0.424 AC XY: 141495 AN XY: 333654

African (AFR) AF: 0.282 AC: 4355 AN: 15426

American (AMR) AF: 0.225 AC: 5147 AN: 22826

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 6156 AN: 16292

East Asian (EAS) AF: 0.269 AC: 8809 AN: 32794

South Asian (SAS) AF: 0.376 AC: 20148 AN: 53552

European-Finnish (FIN) AF: 0.415 AC: 16924 AN: 40820

Middle Eastern (MID) AF: 0.399 AC: 1005 AN: 2518

European-Non Finnish (NFE) AF: 0.462 AC: 193668 AN: 419360

Other (OTH) AF: 0.412 AC: 13024 AN: 31586

GnomAD4 genome AF: 0.375 AC: 54984 AN: 146480 Hom.: 11161 Cov.: 27 AF XY: 0.370 AC XY: 26145 AN XY: 70750

African (AFR) AF: 0.270 AC: 10724 AN: 39786

American (AMR) AF: 0.267 AC: 3901 AN: 14608

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1395 AN: 3444

East Asian (EAS) AF: 0.234 AC: 1170 AN: 5000

South Asian (SAS) AF: 0.365 AC: 1710 AN: 4680

European-Finnish (FIN) AF: 0.377 AC: 3231 AN: 8572

Middle Eastern (MID) AF: 0.417 AC: 116 AN: 278

European-Non Finnish (NFE) AF: 0.470 AC: 31578 AN: 67186

Other (OTH) AF: 0.382 AC: 774 AN: 2028

Alfa AF: 0.268 Hom.: 691

Bravo AF: 0.361

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.31
PhyloP100		0.012
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: rs28438569; hg19: chr15-101109358;