15-100569122-CAAAA-C

Position:

• chr15-100569122-CAAAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001040616.3(LINS1):​c.*112_*115del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 476,348 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (51 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (1 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.973

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 15-100569122-CAAAA-C is Benign according to our data. Variant chr15-100569122-CAAAA-C is described in ClinVar as [Benign]. Clinvar id is 1236361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*112_*115del		3_prime_UTR_variant	7/7	ENST00000314742.13	NP_001035706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINS1	ENST00000314742.13	c.*112_*115del		3_prime_UTR_variant	7/7	5	NM_001040616.3	ENSP00000318423	P1
LINS1	ENST00000560783.1	c.192-3861_192-3858del		intron_variant, NMD_transcript_variant		5		ENSP00000474128

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 1961 AN: 106108 Hom.: 51 Cov.: 0

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00743

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000673

Gnomad FIN AF: 0.000330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.0171

GnomAD4 exome AF: 0.00287 AC: 1061 AN: 370254 Hom.: 1 AF XY: 0.00232 AC XY: 454 AN XY: 195474

Gnomad4 AFR exome AF: 0.0586

Gnomad4 AMR exome AF: 0.00512

Gnomad4 ASJ exome AF: 0.00131

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.000669

Gnomad4 FIN exome AF: 0.000989

Gnomad4 NFE exome AF: 0.000753

Gnomad4 OTH exome AF: 0.00521

GnomAD4 genome AF: 0.0185 AC: 1958 AN: 106094 Hom.: 51 Cov.: 0 AF XY: 0.0192 AC XY: 932 AN XY: 48628

Gnomad4 AFR AF: 0.0672

Gnomad4 AMR AF: 0.00742

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000678

Gnomad4 FIN AF: 0.000330

Gnomad4 NFE AF: 0.000163

Gnomad4 OTH AF: 0.0170

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

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;