Genetic Variant NM_007122.5: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5 link	c.277-80C>G	intron_variant	Intron 5 of 10	ENST00000368021.7	NP_009053.1	P22415-1A0A0S2Z4U5
USF1	NM_001276373.2 link	c.277-80C>G	intron_variant	Intron 5 of 10		NP_001263302.1	P22415-1A0A0S2Z4U5
USF1	NM_207005.3 link	c.100-80C>G	intron_variant	Intron 5 of 10		NP_996888.1	P22415-2
USF1	XM_047429959.1 link	c.100-80C>G	intron_variant	Intron 2 of 7		XP_047285915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7 link	c.277-80C>G		intron_variant	Intron 5 of 10	1	NM_007122.5	ENSP00000357000.3		P22415-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over