Genetic Variant USF1:c.277-80C>G (chr1-161041926-G-C) – 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.277-80C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,441,886 control chromosomes in the GnomAD database, including 417,106 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 0.77 ( 45294 hom., cov: 30)

Exomes 𝑓: 0.76 ( 371812 hom. )

Consequence

USF1
NM_007122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

Publications

25 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 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.277-80C>G	intron	N/A	NP_009053.1	P22415-1
USF1	NM_001276373.2		c.277-80C>G	intron	N/A	NP_001263302.1	A0A0S2Z4U5
USF1	NM_207005.3		c.100-80C>G	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.277-80C>G	intron	N/A	ENSP00000357000.3	P22415-1
USF1	ENST00000368020.5	TSL:1	c.277-80C>G	intron	N/A	ENSP00000356999.1	P22415-1
USF1	ENST00000961613.1		c.277-80C>G	intron	N/A	ENSP00000631672.1

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

117121

AN:

151900

Hom.:

45262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.782

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.751

Gnomad OTH

AF:

0.777

GnomAD4 exome

AF:

0.758

AC:

978032

AN:

1289868

Hom.:

371812

Cov.:

AF XY:

0.757

AC XY:

483464

AN XY:

638638

show subpopulations

African (AFR)

AF:

0.808

AC:

24189

AN:

29936

American (AMR)

AF:

0.791

AC:

30538

AN:

38588

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

16614

AN:

21464

East Asian (EAS)

AF:

0.874

AC:

33503

AN:

38326

South Asian (SAS)

AF:

0.718

AC:

53375

AN:

74382

European-Finnish (FIN)

AF:

0.755

AC:

37747

AN:

50020

Middle Eastern (MID)

AF:

0.781

AC:

4088

AN:

5234

European-Non Finnish (NFE)

AF:

0.754

AC:

737120

AN:

977816

Other (OTH)

AF:

0.755

AC:

40858

AN:

54102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11863

23726

35590

47453

59316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17866

35732

53598

71464

89330

<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:

0.771

AC:

117207

AN:

152018

Hom.:

45294

Cov.:

AF XY:

0.770

AC XY:

57203

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.809

AC:

33504

AN:

41414

American (AMR)

AF:

0.748

AC:

11437

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

2702

AN:

3470

East Asian (EAS)

AF:

0.852

AC:

4400

AN:

5166

South Asian (SAS)

AF:

0.718

AC:

3464

AN:

4822

European-Finnish (FIN)

AF:

0.764

AC:

8087

AN:

10582

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.751

AC:

51034

AN:

67964

Other (OTH)

AF:

0.779

AC:

1643

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1388

2776

4164

5552

6940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.693

Hom.:

1979

Bravo

AF:

0.778

Asia WGS

AF:

0.736

AC:

2562

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.5

(source)

DANN

Benign

0.48

PhyloP100

0.12

PromoterAI

-0.027

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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