rs2843159

Positions:

• chr1-2304233-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003036.4(SKI):​c.1475-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,552,814 control chromosomes in the GnomAD database, including 33,893 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (7559 hom., cov: 33)
  • Exomes 𝑓: 0.18 (26334 hom.)
• Consequence: SKI NM_003036.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.915

Genes affected

SKI (HGNC:10896): (SKI proto-oncogene) This gene encodes the nuclear protooncogene protein homolog of avian sarcoma viral (v-ski) oncogene. It functions as a repressor of TGF-beta signaling, and may play a role in neural tube development and muscle differentiation. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-2304233-C-T is Benign according to our data. Variant chr1-2304233-C-T is described in ClinVar as [Benign]. Clinvar id is 673795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKI	NM_003036.4	c.1475-60C>T		intron_variant		ENST00000378536.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKI	ENST00000378536.5	c.1475-60C>T		intron_variant		1	NM_003036.4	P1
SKI	ENST00000507179.1	n.464-60C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41720 AN: 151928 Hom.: 7540 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.175 AC: 245719 AN: 1400772 Hom.: 26334 Cov.: 36 AF XY: 0.178 AC XY: 123260 AN XY: 691230

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.275 AC: 41787 AN: 152042 Hom.: 7559 Cov.: 33 AF XY: 0.280 AC XY: 20782 AN XY: 74336

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.248

Alfa AF: 0.171 Hom.: 2897

Bravo AF: 0.294

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 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2843159; hg19: chr1-2235672; COSMIC: COSV66013023; COSMIC: COSV66013023;