Genetic Variant NM_021228.3:c.-6-226G>A (chr19-49644795-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

24 publications found

Variant links:

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]

SCAF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Sel.	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	Q9H7N4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCAF1	ENST00000360565.8	TSL:2 MANE Select	c.-6-226G>A	intron	N/A	ENSP00000353769.2	Q9H7N4
SCAF1	ENST00000892599.1		c.-6-226G>A	intron	N/A	ENSP00000562658.1
SCAF1	ENST00000892600.1		c.-6-226G>A	intron	N/A	ENSP00000562659.1

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

65999

AN:

151830

Hom.:

16841

Cov.:

show subpopulations

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.:

AF XY:

0.316

AC XY:

38495

AN XY:

121702

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2322

4644

6965

9287

11609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.435

AC:

66098

AN:

151948

Hom.:

16885

Cov.:

AF XY:

0.426

AC XY:

31651

AN XY:

74284

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1709

3418

5126

6835

8544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.61

PhyloP100

-0.13

PromoterAI

0.0080

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over