rs2073655

Positions:

• chr1-161042800-G-A

Variant summary

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

The NM_007122.5(USF1):​c.58+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,613,734 control chromosomes in the GnomAD database, including 56,395 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 0.22 (4326 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52069 hom.)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF1	NM_007122.5	c.58+33C>T		intron_variant		ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.58+33C>T		intron_variant			NP_001263302.1
USF1	NM_207005.3	c.-89+33C>T		intron_variant			NP_996888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.58+33C>T		intron_variant		1	NM_007122.5	ENSP00000357000	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32990 AN: 152084 Hom.: 4323 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.242

GnomAD3 exomes AF: 0.250 AC: 62800 AN: 251476 Hom.: 8558 AF XY: 0.250 AC XY: 33950 AN XY: 135908

Gnomad AFR exome AF: 0.0624

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.181

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.356

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.262 AC: 382862 AN: 1461532 Hom.: 52069 Cov.: 35 AF XY: 0.261 AC XY: 189574 AN XY: 727088

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.217 AC: 32987 AN: 152202 Hom.: 4326 Cov.: 32 AF XY: 0.218 AC XY: 16191 AN XY: 74422

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.240

Alfa AF: 0.252 Hom.: 1280

Bravo AF: 0.206

Asia WGS AF: 0.146 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs2073655; hg19: chr1-161012590; COSMIC: COSV57037849; COSMIC: COSV57037849;