Genetic Variant USF1:c.473-116T>C (chr1-161041527-A-G) – 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.473-116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,469,900 control chromosomes in the GnomAD database, including 392,853 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 0.75 ( 43309 hom., cov: 30)

Exomes 𝑓: 0.73 ( 349544 hom. )

Consequence

USF1
NM_007122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320

Publications

9 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 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.473-116T>C	intron	N/A	NP_009053.1	P22415-1
USF1	NM_001276373.2		c.473-116T>C	intron	N/A	NP_001263302.1	A0A0S2Z4U5
USF1	NM_207005.3		c.296-116T>C	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.473-116T>C	intron	N/A	ENSP00000357000.3	P22415-1
USF1	ENST00000368020.5	TSL:1	c.473-116T>C	intron	N/A	ENSP00000356999.1	P22415-1
USF1	ENST00000961613.1		c.473-116T>C	intron	N/A	ENSP00000631672.1

Frequencies

GnomAD3 genomes

AF:

0.753

AC:

114290

AN:

151836

Hom.:

43272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.824

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.744

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.763

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.714

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.727

AC:

958073

AN:

1317946

Hom.:

349544

Cov.:

AF XY:

0.726

AC XY:

472841

AN XY:

651220

show subpopulations

African (AFR)

AF:

0.825

AC:

25005

AN:

30316

American (AMR)

AF:

0.767

AC:

26410

AN:

34436

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

16253

AN:

22130

East Asian (EAS)

AF:

0.875

AC:

32996

AN:

37704

South Asian (SAS)

AF:

0.696

AC:

52569

AN:

75556

European-Finnish (FIN)

AF:

0.754

AC:

37848

AN:

50200

Middle Eastern (MID)

AF:

0.741

AC:

2870

AN:

3874

European-Non Finnish (NFE)

AF:

0.718

AC:

724333

AN:

1008794

Other (OTH)

AF:

0.724

AC:

39789

AN:

54936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13197

26394

39592

52789

65986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18196

36392

54588

72784

90980

<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:

0.753

AC:

114381

AN:

151954

Hom.:

43309

Cov.:

AF XY:

0.753

AC XY:

55902

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.824

AC:

34112

AN:

41418

American (AMR)

AF:

0.713

AC:

10877

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.744

AC:

2580

AN:

3470

East Asian (EAS)

AF:

0.853

AC:

4407

AN:

5168

South Asian (SAS)

AF:

0.705

AC:

3388

AN:

4806

European-Finnish (FIN)

AF:

0.763

AC:

8073

AN:

10576

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.714

AC:

48481

AN:

67946

Other (OTH)

AF:

0.753

AC:

1585

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1445

2890

4336

5781

7226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.739

Hom.:

8999

Bravo

AF:

0.758

Asia WGS

AF:

0.744

AC:

2591

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

(source)

DANN

Benign

0.44

PhyloP100

-0.32

PromoterAI

-0.017

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