11-15253696-A-G

Variant names:

• chr11-15253696-A-G
• rs939046
• XM_017017698.2:c.1470+13173A>G

Variant summary

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

The XM_017017698.2(INSC):​c.1470+13173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,554 control chromosomes in the GnomAD database, including 7,411 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 0.29 (7411 hom., cov: 30)
• Consequence: INSC XM_017017698.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSC	XM_017017698.2	c.1470+13173A>G		intron_variant	Intron 12 of 12		XP_016873187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43903 AN: 151438 Hom.: 7406 Cov.: 30

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.290 AC: 43923 AN: 151554 Hom.: 7411 Cov.: 30 AF XY: 0.299 AC XY: 22147 AN XY: 73956

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.328

Alfa AF: 0.314 Hom.: 7565

Bravo AF: 0.283

Asia WGS AF: 0.513 AC: 1783 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.1
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs939046; hg19: chr11-15275242;