19-49644795-G-A

Variant names:

• chr19-49644795-G-A
• rs12104272
• NM_021228.3:c.-6-226G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021228.3. 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
	SCAF1	NM_021228.3	MANE Select	c.-6-226G>A		intron	N/A	NP_067051.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF1	ENST00000360565.8	TSL:2 MANE Select	c.-6-226G>A		intron	N/A	ENSP00000353769.2
	SCAF1	ENST00000598359.5	TSL:3	c.-6-226G>A		intron	N/A	ENSP00000473210.1
	SCAF1	ENST00000595242.3	TSL:3	c.-232G>A		upstream_gene	N/A	ENSP00000472276.1

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

African (AFR) AF: 0.718 AC: 4337 AN: 6042

American (AMR) AF: 0.348 AC: 2439 AN: 7004

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 2654 AN: 8358

East Asian (EAS) AF: 0.253 AC: 4512 AN: 17840

South Asian (SAS) AF: 0.305 AC: 4402 AN: 14410

European-Finnish (FIN) AF: 0.250 AC: 4261 AN: 17070

Middle Eastern (MID) AF: 0.413 AC: 475 AN: 1150

European-Non Finnish (NFE) AF: 0.312 AC: 46416 AN: 148580

Other (OTH) AF: 0.354 AC: 5283 AN: 14918

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

African (AFR) AF: 0.727 AC: 30119 AN: 41430

American (AMR) AF: 0.378 AC: 5771 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3464

East Asian (EAS) AF: 0.274 AC: 1417 AN: 5180

South Asian (SAS) AF: 0.332 AC: 1597 AN: 4806

European-Finnish (FIN) AF: 0.252 AC: 2662 AN: 10556

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21997 AN: 67936

Other (OTH) AF: 0.417 AC: 879 AN: 2106

Alfa AF: 0.361 Hom.: 13113

Bravo AF: 0.458

Asia WGS AF: 0.398 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.47
DANN	Benign	0.61
PhyloP100		-0.13
PromoterAI		0.0080	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12104272; hg19: chr19-50148052;