Genetic Variant SF1-DT:n.21-28C>T (chr11-64778919-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000594089.2(SF1-DT):n.21-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 167,946 control chromosomes in the GnomAD database, including 48,517 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 0.71 ( 42967 hom., cov: 31)

Exomes 𝑓: 0.82 ( 5550 hom. )

Consequence

SF1-DT
ENST00000594089.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.291

Publications

41 publications found

Variant links:

Genes affected

SF1-DT (HGNC:55278): (SF1 divergent transcript)

SF1-DT links:

SF1 (HGNC:12950): (splicing factor 1) This gene encodes a nuclear pre-mRNA splicing factor. The encoded protein specifically recognizes the intron branch point sequence at the 3' splice site, together with the large subunit of U2 auxiliary factor (U2AF), and is required for the early stages of spliceosome assembly. It also plays a role in nuclear pre-mRNA retention and transcriptional repression. The encoded protein contains an N-terminal U2AF ligand motif, a central hnRNP K homology motif and quaking 2 region which bind a key branch-site adenosine within the branch point sequence, a zinc knuckles domain, and a C-terminal proline-rich domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

SF1 links:

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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=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594089.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SF1-DT	ENST00000594089.2	TSL:6	n.21-28C>T	intron	N/A
SF1	ENST00000334944.9	TSL:1	c.-527G>A	upstream_gene	N/A	ENSP00000334414.5	Q15637-2
SF1	ENST00000377394.7	TSL:1	c.-527G>A	upstream_gene	N/A	ENSP00000366611.3	Q15637-6

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108588

AN:

151914

Hom.:

42968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.967

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.648

Gnomad SAS

AF:

0.784

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.823

AC:

13095

AN:

15914

Hom.:

5550

Cov.:

AF XY:

0.827

AC XY:

6899

AN XY:

8346

show subpopulations

African (AFR)

AF:

0.317

AC:

128

AN:

404

American (AMR)

AF:

0.610

AC:

238

AN:

390

Ashkenazi Jewish (ASJ)

AF:

0.839

AC:

483

AN:

576

East Asian (EAS)

AF:

0.544

AC:

882

AN:

1622

South Asian (SAS)

AF:

0.723

AC:

107

AN:

148

European-Finnish (FIN)

AF:

0.876

AC:

1432

AN:

1634

Middle Eastern (MID)

AF:

0.833

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.889

AC:

8955

AN:

10068

Other (OTH)

AF:

0.809

AC:

780

AN:

964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

192

289

385

481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.714

AC:

108619

AN:

152032

Hom.:

42967

Cov.:

AF XY:

0.714

AC XY:

53053

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.358

AC:

14822

AN:

41400

American (AMR)

AF:

0.691

AC:

10558

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.850

AC:

2950

AN:

3472

East Asian (EAS)

AF:

0.648

AC:

3348

AN:

5166

South Asian (SAS)

AF:

0.784

AC:

3776

AN:

4818

European-Finnish (FIN)

AF:

0.888

AC:

9400

AN:

10584

Middle Eastern (MID)

AF:

0.847

AC:

249

AN:

294

European-Non Finnish (NFE)

AF:

0.898

AC:

61053

AN:

67990

Other (OTH)

AF:

0.748

AC:

1581

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1142

2283

3425

4566

5708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.821

Hom.:

87385

Bravo

AF:

0.684

Asia WGS

AF:

0.686

AC:

2383

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.9

(source)

DANN

Benign

0.81

PhyloP100

-0.29

PromoterAI

0.013

Neutral

(source)

Splicing

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