rs3737787

Variant names:

• chr1-161039733-G-A
• rs3737787
• NM_007122.5:c.*187C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007122.5(USF1):​c.*187C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 626,724 control chromosomes in the GnomAD database, including 20,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (4277 hom., cov: 32)
  • Exomes 𝑓: 0.26 (16626 hom.)
• Consequence: USF1 NM_007122.5 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -3.21
• Publications: 52 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	NM_007122.5	MANE Select	c.*187C>T		3_prime_UTR	Exon 11 of 11	NP_009053.1	P22415-1
	USF1	NM_001276373.2		c.*187C>T		3_prime_UTR	Exon 11 of 11	NP_001263302.1	A0A0S2Z4U5
	USF1	NM_207005.3		c.*187C>T		3_prime_UTR	Exon 11 of 11	NP_996888.1	P22415-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	ENST00000368021.7	TSL:1 MANE Select	c.*187C>T		3_prime_UTR	Exon 11 of 11	ENSP00000357000.3	P22415-1
	USF1	ENST00000368020.5	TSL:1	c.*187C>T		3_prime_UTR	Exon 11 of 11	ENSP00000356999.1	P22415-1
	USF1	ENST00000961613.1		c.*187C>T		3_prime_UTR	Exon 11 of 11	ENSP00000631672.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32677 AN: 152038 Hom.: 4274 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.256 AC: 121703 AN: 474568 Hom.: 16626 Cov.: 5 AF XY: 0.251 AC XY: 62833 AN XY: 250274

African (AFR) AF: 0.0654 AC: 845 AN: 12912

American (AMR) AF: 0.255 AC: 4995 AN: 19564

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 4100 AN: 13754

East Asian (EAS) AF: 0.204 AC: 6229 AN: 30494

South Asian (SAS) AF: 0.139 AC: 6524 AN: 46964

European-Finnish (FIN) AF: 0.351 AC: 10328 AN: 29402

Middle Eastern (MID) AF: 0.264 AC: 525 AN: 1986

European-Non Finnish (NFE) AF: 0.278 AC: 81529 AN: 292888

Other (OTH) AF: 0.249 AC: 6628 AN: 26604

GnomAD4 genome AF: 0.215 AC: 32677 AN: 152156 Hom.: 4277 Cov.: 32 AF XY: 0.215 AC XY: 16011 AN XY: 74376

African (AFR) AF: 0.0625 AC: 2596 AN: 41546

American (AMR) AF: 0.249 AC: 3800 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1060 AN: 3468

East Asian (EAS) AF: 0.183 AC: 949 AN: 5180

South Asian (SAS) AF: 0.145 AC: 700 AN: 4834

European-Finnish (FIN) AF: 0.352 AC: 3711 AN: 10554

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18948 AN: 67984

Other (OTH) AF: 0.240 AC: 506 AN: 2104

Alfa AF: 0.254 Hom.: 16665

Bravo AF: 0.205

Asia WGS AF: 0.133 AC: 469 AN: 3478

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Hyperlipidemia, familial combined, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.82
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs3737787; hg19: chr1-161009523;