rs12104272

Positions:

• chr19-49644795-G-A

Variant summary

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

The NM_021228.3(SCAF1):​c.-6-226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 387,320 control chromosomes in the GnomAD database, including 29,966 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 0.44 (16885 hom., cov: 31)
  • Exomes 𝑓: 0.32 (13081 hom.)
• Consequence: SCAF1 NM_021228.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

Genes affected

SCAF1 (HGNC:30403): (SR-related CTD associated factor 1) Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.-6-226G>A		intron_variant		ENST00000360565.8	NP_067051.2
SCAF1	XM_005259122.6	c.-6-226G>A		intron_variant			XP_005259179.1
SCAF1	XM_011527194.4	c.4-226G>A		intron_variant			XP_011525496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8	c.-6-226G>A		intron_variant		2	NM_021228.3	ENSP00000353769	P1
SCAF1	ENST00000598359.5	c.-6-226G>A		intron_variant		3		ENSP00000473210
SCAF1	ENST00000601038.5			upstream_gene_variant		3		ENSP00000472649

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65999 AN: 151830 Hom.: 16841 Cov.: 31

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.318 AC: 74779 AN: 235372 Hom.: 13081 Cov.: 2 AF XY: 0.316 AC XY: 38495 AN XY: 121702

Gnomad4 AFR exome AF: 0.718

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.435 AC: 66098 AN: 151948 Hom.: 16885 Cov.: 31 AF XY: 0.426 AC XY: 31651 AN XY: 74284

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.417

Alfa AF: 0.350 Hom.: 7835

Bravo AF: 0.458

Asia WGS AF: 0.398 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.47
DANN	Benign	0.61

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: rs12104272; hg19: chr19-50148052;