NM_007122.5:c.-56G>A

Variant names:

• chr1-161043331-C-T
• rs2516839
• NM_007122.5:c.-56G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_007122.5(USF1):​c.-56G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,613,404 control chromosomes in the GnomAD database, including 272,604 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 0.49 (19960 hom., cov: 32)
  • Exomes 𝑓: 0.58 (252644 hom.)
• Consequence: USF1 NM_007122.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 62 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.61 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	NM_007122.5	MANE Select	c.-56G>A		5_prime_UTR	Exon 2 of 11	NP_009053.1
	USF1	NM_001276373.2		c.-56G>A		5_prime_UTR	Exon 2 of 11	NP_001263302.1
	USF1	NM_207005.3		c.-202G>A		5_prime_UTR	Exon 2 of 11	NP_996888.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	ENST00000368021.7	TSL:1 MANE Select	c.-56G>A		5_prime_UTR	Exon 2 of 11	ENSP00000357000.3
	USF1	ENST00000368020.5	TSL:1	c.-56G>A		5_prime_UTR	Exon 2 of 11	ENSP00000356999.1
	USF1	ENST00000473969.6	TSL:5	n.-56G>A		non_coding_transcript_exon	Exon 2 of 11	ENSP00000435671.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74205 AN: 151892 Hom.: 19959 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.581 AC: 849309 AN: 1461392 Hom.: 252644 Cov.: 39 AF XY: 0.579 AC XY: 421134 AN XY: 727018

African (AFR) AF: 0.241 AC: 8052 AN: 33456

American (AMR) AF: 0.424 AC: 18939 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 15032 AN: 26122

East Asian (EAS) AF: 0.327 AC: 12993 AN: 39686

South Asian (SAS) AF: 0.465 AC: 40060 AN: 86192

European-Finnish (FIN) AF: 0.610 AC: 32597 AN: 53406

Middle Eastern (MID) AF: 0.542 AC: 3122 AN: 5756

European-Non Finnish (NFE) AF: 0.617 AC: 685504 AN: 1111750

Other (OTH) AF: 0.547 AC: 33010 AN: 60368

GnomAD4 genome AF: 0.488 AC: 74225 AN: 152012 Hom.: 19960 Cov.: 32 AF XY: 0.486 AC XY: 36083 AN XY: 74274

African (AFR) AF: 0.257 AC: 10673 AN: 41462

American (AMR) AF: 0.474 AC: 7239 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2037 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1707 AN: 5176

South Asian (SAS) AF: 0.473 AC: 2273 AN: 4802

European-Finnish (FIN) AF: 0.626 AC: 6601 AN: 10538

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41814 AN: 67968

Other (OTH) AF: 0.519 AC: 1095 AN: 2108

Alfa AF: 0.537 Hom.: 8882

Bravo AF: 0.470

Asia WGS AF: 0.354 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		0.062
PromoterAI		0.060	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2516839; hg19: chr1-161013121; COSMIC: COSV57041547; COSMIC: COSV57041547;