rs12045693

Variant names:

• chr1-2274142-C-A
• rs12045693
• NM_003036.4:c.970-28836C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2274142-C-A
• chr1-2274142-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

SKI Gene-Disease associations (from GenCC):

• Shprintzen-Goldberg syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, G2P, Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003036.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	NM_003036.4	MANE Select	c.970-28836C>A		intron	N/A	NP_003027.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	ENST00000378536.5	TSL:1 MANE Select	c.970-28836C>A		intron	N/A	ENSP00000367797.4
	SKI	ENST00000478223.2	TSL:3	n.76+26071C>A		intron	N/A
	SKI	ENST00000508416.1	TSL:3	n.192-28836C>A		intron	N/A

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

African (AFR) AF: 0.507 AC: 20977 AN: 41336

American (AMR) AF: 0.488 AC: 7419 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3468

East Asian (EAS) AF: 0.494 AC: 2552 AN: 5170

South Asian (SAS) AF: 0.370 AC: 1751 AN: 4728

European-Finnish (FIN) AF: 0.461 AC: 4825 AN: 10466

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28682 AN: 67840

Other (OTH) AF: 0.419 AC: 884 AN: 2108

Alfa AF: 0.440 Hom.: 27058

Bravo AF: 0.460

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.28
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12045693; hg19: chr1-2205581; COSMIC: COSV66014733;