18-47230050-A-C

Position:

• chr18-47230050-A-C

Variant summary

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

The NM_001278063.4(SKOR2):​c.2917+409T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,062 control chromosomes in the GnomAD database, including 14,425 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 0.43 (14425 hom., cov: 32)
• Consequence: SKOR2 NM_001278063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

Genes affected

SKOR2 (HGNC:32695): (SKI family transcriptional corepressor 2) Enables SMAD binding activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKOR2	NM_001278063.4	c.2917+409T>G		intron_variant		ENST00000425639.3	NP_001264992.1
SKOR2	XM_047437757.1	c.2917+409T>G		intron_variant			XP_047293713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKOR2	ENST00000425639.3	c.2917+409T>G		intron_variant		5	NM_001278063.4	ENSP00000414750.3
SKOR2	ENST00000620245.4	c.2917+409T>G		intron_variant		5		ENSP00000483333.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65693 AN: 151944 Hom.: 14420 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.432 AC: 65709 AN: 152062 Hom.: 14425 Cov.: 32 AF XY: 0.432 AC XY: 32078 AN XY: 74338

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.453

Alfa AF: 0.366 Hom.: 1923

Bravo AF: 0.426

Asia WGS AF: 0.280 AC: 973 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8086549; hg19: chr18-44756421;