chr15-100569122-CAAA-C

Variant names:

• chr15-100569122-CAAA-C
• rs56225071
• NM_001040616.3:c.*113_*115delTTT

Variant summary

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

The NM_001040616.3(LINS1):​c.*113_*115delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 474,252 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 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0032 (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 = 0.00318 (1171/368160) while in subpopulation EAS AF= 0.00567 (142/25026). AF 95% confidence interval is 0.00491. There are 0 homozygotes in gnomad4_exome. There are 610 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.*113_*115delTTT		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.*113_*115delTTT		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3860_191-3858delTTT		intron_variant	Intron 1 of 3	5		ENSP00000474128.1
LINS1	ENST00000559169.1	n.*110_*112delTTT		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000123 AC: 13 AN: 106106 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000182

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00318 AC: 1171 AN: 368160 Hom.: 0 AF XY: 0.00314 AC XY: 610 AN XY: 194406

Gnomad4 AFR exome AF: 0.00438

Gnomad4 AMR exome AF: 0.00420

Gnomad4 ASJ exome AF: 0.00450

Gnomad4 EAS exome AF: 0.00567

Gnomad4 SAS exome AF: 0.00183

Gnomad4 FIN exome AF: 0.00263

Gnomad4 NFE exome AF: 0.00294

Gnomad4 OTH exome AF: 0.00376

GnomAD4 genome AF: 0.000123 AC: 13 AN: 106092 Hom.: 0 Cov.: 0 AF XY: 0.000103 AC XY: 5 AN XY: 48628

Gnomad4 AFR AF: 0.000363

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.0000182

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;