rs11288195

Variant names:

• chr3-170374265-AG-A
• rs11288195
• NM_005414.5:c.1099-6977delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005414.5(SKIL):​c.1099-6977delG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52975 hom., cov: 0)
• Consequence: SKIL NM_005414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 publications found

Genes affected

SKIL (HGNC:10897): (SKI like proto-oncogene) The protein encoded by this gene is a component of the SMAD pathway, which regulates cell growth and differentiation through transforming growth factor-beta (TGFB). In the absence of ligand, the encoded protein binds to the promoter region of TGFB-responsive genes and recruits a nuclear repressor complex. TGFB signaling causes SMAD3 to enter the nucleus and degrade this protein, allowing these genes to be activated. Four transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIL	NM_005414.5	c.1099-6977delG		intron_variant	Intron 2 of 6	ENST00000259119.9	NP_005405.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIL	ENST00000259119.9	c.1099-6978delG		intron_variant	Intron 2 of 6	1	NM_005414.5	ENSP00000259119.4

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126454 AN: 151868 Hom.: 52961 Cov.: 0

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.832 AC: 126511 AN: 151988 Hom.: 52975 Cov.: 0 AF XY: 0.836 AC XY: 62074 AN XY: 74294

African (AFR) AF: 0.723 AC: 29919 AN: 41394

American (AMR) AF: 0.845 AC: 12901 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3038 AN: 3466

East Asian (EAS) AF: 0.942 AC: 4879 AN: 5180

South Asian (SAS) AF: 0.854 AC: 4122 AN: 4826

European-Finnish (FIN) AF: 0.918 AC: 9695 AN: 10566

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59180 AN: 67970

Other (OTH) AF: 0.823 AC: 1736 AN: 2110

Alfa AF: 0.843 Hom.: 6603

Bravo AF: 0.824

Asia WGS AF: 0.847 AC: 2937 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11288195; hg19: chr3-170092053;