rs2073658

Positions:

• chr1-161040972-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007122.5(USF1):​c.561-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,466,922 control chromosomes in the GnomAD database, including 50,584 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 0.22 (4290 hom., cov: 31)
  • Exomes 𝑓: 0.26 (46294 hom.)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.45

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF1	NM_007122.5	c.561-100G>A		intron_variant		ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.561-100G>A		intron_variant			NP_001263302.1
USF1	NM_207005.3	c.384-100G>A		intron_variant			NP_996888.1
USF1	XM_047429959.1	c.384-100G>A		intron_variant			XP_047285915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.561-100G>A		intron_variant		1	NM_007122.5	ENSP00000357000	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32772 AN: 151874 Hom.: 4287 Cov.: 31

Gnomad AFR AF: 0.0653

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: 0.242

GnomAD4 exome AF: 0.259 AC: 341020 AN: 1314930 Hom.: 46294 AF XY: 0.257 AC XY: 168312 AN XY: 654562

Gnomad4 AFR exome AF: 0.0598

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.216 AC: 32772 AN: 151992 Hom.: 4290 Cov.: 31 AF XY: 0.216 AC XY: 16033 AN XY: 74278

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.239

Alfa AF: 0.262 Hom.: 5292

Bravo AF: 0.206

Asia WGS AF: 0.133 AC: 469 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hyperlipidemia, familial combined, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2073658; hg19: chr1-161010762;