11-15240775-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042536.3(INSC):c.1470+252C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,026 control chromosomes in the GnomAD database, including 23,551 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23551 hom., cov: 32)
• Consequence: INSC NM_001042536.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

Genes affected

INSC (HGNC:33116): (INSC spindle orientation adaptor protein) In Drosophila, neuroblasts divide asymmetrically into another neuroblast at the apical side and a smaller ganglion mother cell on the basal side. Cell polarization is precisely regulated by 2 apically localized multiprotein signaling complexes that are tethered by Inscuteable, which regulates their apical localization (Izaki et al., 2006 [PubMed 16458856]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSC	NM_001042536.3	c.1470+252C>G		intron_variant		ENST00000379556.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSC	ENST00000379556.8	c.1470+252C>G		intron_variant		1	NM_001042536.3	P1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83668 AN: 151908 Hom.: 23534 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.551 AC: 83743 AN: 152026 Hom.: 23551 Cov.: 32 AF XY: 0.551 AC XY: 40935 AN XY: 74296

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.585

Alfa AF: 0.556 Hom.: 2935

Bravo AF: 0.548

Asia WGS AF: 0.690 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.9
Dann	Benign	0.69

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: rs7116710; hg19: chr11-15262321;