Genetic Variant USF1:c.-86+999T>C (chr1-161044859-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.-86+999T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,418 control chromosomes in the GnomAD database, including 8,566 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 0.28 ( 8558 hom., cov: 32)

Exomes 𝑓: 0.21 ( 8 hom. )

Consequence

USF1
NM_007122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.350

Publications

18 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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 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.-86+999T>C	intron	N/A	NP_009053.1	P22415-1
USF1	NM_001276373.2		c.-86+53T>C	intron	N/A	NP_001263302.1	A0A0S2Z4U5
USF1	NM_207005.3		c.-232+999T>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.-86+999T>C	intron	N/A	ENSP00000357000.3	P22415-1
USF1	ENST00000368020.5	TSL:1	c.-86+53T>C	intron	N/A	ENSP00000356999.1	P22415-1
USF1	ENST00000961613.1		c.-86+146T>C	intron	N/A	ENSP00000631672.1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42700

AN:

151950

Hom.:

8539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.209

AC:

AN:

350

Hom.:

AF XY:

0.182

AC XY:

AN XY:

170

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.540

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.147

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.124

AC:

AN:

226

Other (OTH)

AF:

0.389

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.281

AC:

42763

AN:

152068

Hom.:

8558

Cov.:

AF XY:

0.282

AC XY:

20968

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.548

AC:

22701

AN:

41448

American (AMR)

AF:

0.273

AC:

4166

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

660

AN:

3470

East Asian (EAS)

AF:

0.522

AC:

2700

AN:

5170

South Asian (SAS)

AF:

0.246

AC:

1183

AN:

4816

European-Finnish (FIN)

AF:

0.136

AC:

1441

AN:

10580

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9218

AN:

67998

Other (OTH)

AF:

0.258

AC:

544

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1291

2582

3874

5165

6456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.245

Hom.:

5237

Bravo

AF:

0.307

Asia WGS

AF:

0.384

AC:

1334

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.6

(source)

DANN

Benign

0.84

PhyloP100

-0.35

PromoterAI

0.0038

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