chr15-100569122-CAA-C

Variant names:

• chr15-100569122-CAA-C
• rs56225071
• NM_001040616.3:c.*114_*115delTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001040616.3(LINS1):​c.*114_*115delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00881 in 468,770 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 0)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0114 (4124/362678) while in subpopulation EAS AF= 0.0249 (603/24206). AF 95% confidence interval is 0.0233. There are 0 homozygotes in gnomad4_exome. There are 2172 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*114_*115delTT		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	c.*114_*115delTT		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3859_191-3858delTT		intron_variant	Intron 1 of 3	5		ENSP00000474128.1
LINS1	ENST00000559169.1	n.*111_*112delTT		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000471 AC: 5 AN: 106092 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000545

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0114 AC: 4124 AN: 362678 Hom.: 0 AF XY: 0.0113 AC XY: 2172 AN XY: 191544

Gnomad4 AFR exome AF: 0.00942

Gnomad4 AMR exome AF: 0.0137

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.0249

Gnomad4 SAS exome AF: 0.00908

Gnomad4 FIN exome AF: 0.0127

Gnomad4 NFE exome AF: 0.00988

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0000471 AC: 5 AN: 106092 Hom.: 0 Cov.: 0 AF XY: 0.0000617 AC XY: 3 AN XY: 48614

Gnomad4 AFR AF: 0.0000363

Gnomad4 AMR AF: 0.000108

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000545

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs56225071; hg19: chr15-101109327;