Genetic Variant USF1:c.561-100G>A (chr1-161040972-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 NM_007122.5(USF1):c.561-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,466,922 control chromosomes in the GnomAD database, including 50,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.22 ( 4290 hom., cov: 31)

Exomes 𝑓: 0.26 ( 46294 hom. )

Consequence

USF1
NM_007122.5 intron

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 1.45

Publications

37 publications found

Variant links:

Genes affected

USF1 (HGNC:12593): (upstream transcription factor 1) This gene encodes a member of the basic helix-loop-helix leucine zipper family, and can function as a cellular transcription factor. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. This gene has been linked to familial combined hyperlipidemia (FCHL). Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been defined on chromosome 21. [provided by RefSeq, Feb 2013]

USF1 Gene-Disease associations (from GenCC):

hyperlipidemia, combined, 1
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

USF1 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USF1	NM_007122.5	MANE Select	c.561-100G>A	intron	N/A	NP_009053.1	P22415-1
USF1	NM_001276373.2		c.561-100G>A	intron	N/A	NP_001263302.1	A0A0S2Z4U5
USF1	NM_207005.3		c.384-100G>A	intron	N/A	NP_996888.1	P22415-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USF1	ENST00000368021.7	TSL:1 MANE Select	c.561-100G>A	intron	N/A	ENSP00000357000.3	P22415-1
USF1	ENST00000368020.5	TSL:1	c.561-100G>A	intron	N/A	ENSP00000356999.1	P22415-1
USF1	ENST00000961613.1		c.561-100G>A	intron	N/A	ENSP00000631672.1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32772

AN:

151874

Hom.:

4287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.259

AC:

341020

AN:

1314930

Hom.:

46294

AF XY:

0.257

AC XY:

168312

AN XY:

654562

show subpopulations

African (AFR)

AF:

0.0598

AC:

1834

AN:

30680

American (AMR)

AF:

0.254

AC:

9537

AN:

37516

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

6874

AN:

23130

East Asian (EAS)

AF:

0.201

AC:

7711

AN:

38400

South Asian (SAS)

AF:

0.137

AC:

10625

AN:

77406

European-Finnish (FIN)

AF:

0.350

AC:

15442

AN:

44102

Middle Eastern (MID)

AF:

0.253

AC:

1282

AN:

5066

European-Non Finnish (NFE)

AF:

0.273

AC:

274220

AN:

1003264

Other (OTH)

AF:

0.244

AC:

13495

AN:

55366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11846

23692

35538

47384

59230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8746

17492

26238

34984

43730

<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:

0.216

AC:

32772

AN:

151992

Hom.:

4290

Cov.:

AF XY:

0.216

AC XY:

16033

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.0652

AC:

2703

AN:

41484

American (AMR)

AF:

0.249

AC:

3798

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1058

AN:

3460

East Asian (EAS)

AF:

0.184

AC:

952

AN:

5172

South Asian (SAS)

AF:

0.145

AC:

700

AN:

4818

European-Finnish (FIN)

AF:

0.352

AC:

3710

AN:

10546

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18938

AN:

67934

Other (OTH)

AF:

0.239

AC:

505

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1233

2466

3700

4933

6166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.243

Hom.:

6758

Bravo

AF:

0.206

Asia WGS

AF:

0.133

AC:

469

AN:

3478

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyperlipidemia, familial combined, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.9

(source)

DANN

Benign

0.68

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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