Genetic Variant NM_007122.5:c.9-88A>G (chr1-161042970-T-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.9-88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,569,120 control chromosomes in the GnomAD database, including 38,932 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 ( 8633 hom., cov: 32)

Exomes 𝑓: 0.18 ( 30299 hom. )

Consequence

USF1
NM_007122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.54

Publications

15 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5 link	c.9-88A>G	intron_variant	Intron 2 of 10	ENST00000368021.7	NP_009053.1	P22415-1A0A0S2Z4U5
USF1	NM_001276373.2 link	c.9-88A>G	intron_variant	Intron 2 of 10		NP_001263302.1	P22415-1A0A0S2Z4U5
USF1	NM_207005.3 link	c.-138-88A>G	intron_variant	Intron 2 of 10		NP_996888.1	P22415-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7 link	c.9-88A>G		intron_variant	Intron 2 of 10	1	NM_007122.5	ENSP00000357000.3		P22415-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42878

AN:

152002

Hom.:

8614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.258

GnomAD4 exome

AF:

0.177

AC:

251344

AN:

1417000

Hom.:

30299

AF XY:

0.178

AC XY:

126017

AN XY:

707394

show subpopulations

African (AFR)

AF:

0.567

AC:

18509

AN:

32666

American (AMR)

AF:

0.367

AC:

16359

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

5098

AN:

25860

East Asian (EAS)

AF:

0.547

AC:

21577

AN:

39454

South Asian (SAS)

AF:

0.255

AC:

21733

AN:

85216

European-Finnish (FIN)

AF:

0.143

AC:

7617

AN:

53202

Middle Eastern (MID)

AF:

0.235

AC:

1337

AN:

5682

European-Non Finnish (NFE)

AF:

0.137

AC:

146849

AN:

1071450

Other (OTH)

AF:

0.208

AC:

12265

AN:

58932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

10346

20692

31038

41384

51730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5768

11536

17304

23072

28840

<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:

0.282

AC:

42942

AN:

152120

Hom.:

8633

Cov.:

AF XY:

0.283

AC XY:

21049

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.550

AC:

22818

AN:

41464

American (AMR)

AF:

0.273

AC:

4172

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

662

AN:

3466

East Asian (EAS)

AF:

0.522

AC:

2705

AN:

5182

South Asian (SAS)

AF:

0.247

AC:

1189

AN:

4820

European-Finnish (FIN)

AF:

0.137

AC:

1446

AN:

10588

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9252

AN:

67998

Other (OTH)

AF:

0.259

AC:

548

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1322

2643

3965

5286

6608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.190

Hom.:

14848

Bravo

AF:

0.308

Asia WGS

AF:

0.385

AC:

1340

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0040

(source)

DANN

Benign

0.73

PhyloP100

-5.5

PromoterAI

-0.022

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over