rs12045693

Positions:

• chr1-2274142-C-A
• chr1-2274142-C-G

Variant summary

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

The NM_003036.4(SKI):​c.970-28836C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,504 control chromosomes in the GnomAD database, including 15,761 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 0.45 (15761 hom., cov: 33)
• Consequence: SKI NM_003036.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKI	NM_003036.4	c.970-28836C>A		intron_variant		ENST00000378536.5	NP_003027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKI	ENST00000378536.5	c.970-28836C>A		intron_variant		1	NM_003036.4	ENSP00000367797	P1
SKI	ENST00000478223.2	n.76+26071C>A		intron_variant, non_coding_transcript_variant		3
SKI	ENST00000508416.1	n.192-28836C>A		intron_variant, non_coding_transcript_variant		3
SKI	ENST00000704337.1	n.138-28836C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68641 AN: 151386 Hom.: 15724 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.454 AC: 68736 AN: 151504 Hom.: 15761 Cov.: 33 AF XY: 0.453 AC XY: 33513 AN XY: 73998

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.419

Alfa AF: 0.436 Hom.: 5951

Bravo AF: 0.460

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12045693; hg19: chr1-2205581; COSMIC: COSV66014733;