15-100568921-T-C

Position:

• chr15-100568921-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040616.3(LINS1):​c.*317A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 228,660 control chromosomes in the GnomAD database, including 37,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24201 hom., cov: 29)
  • Exomes 𝑓: 0.59 (13774 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.23

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 15-100568921-T-C is Benign according to our data. Variant chr15-100568921-T-C is described in ClinVar as [Benign]. Clinvar id is 1220592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*317A>G		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.*317A>G		3_prime_UTR_variant	7/7	5	NM_001040616.3	ENSP00000318423	P1
LINS1	ENST00000560783.1	c.192-3656A>G		intron_variant, NMD_transcript_variant		5		ENSP00000474128

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84447 AN: 151578 Hom.: 24187 Cov.: 29

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.585 AC: 45062 AN: 76966 Hom.: 13774 Cov.: 0 AF XY: 0.582 AC XY: 24568 AN XY: 42214

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.559

GnomAD4 genome AF: 0.557 AC: 84510 AN: 151694 Hom.: 24201 Cov.: 29 AF XY: 0.557 AC XY: 41277 AN XY: 74092

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.568

Alfa AF: 0.599 Hom.: 3483

Bravo AF: 0.543

Asia WGS AF: 0.490 AC: 1707 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.35

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: rs3751547; hg19: chr15-101109126;