rs2516839

chr1-161043331-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USF1	NM_007122.5	c.-56G>A		5_prime_UTR_variant	2/11	ENST00000368021.7
USF1	NM_001276373.2	c.-56G>A		5_prime_UTR_variant	2/11
USF1	NM_207005.3	c.-202G>A		5_prime_UTR_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF1	ENST00000368021.7	c.-56G>A		5_prime_UTR_variant	2/11	1	NM_007122.5	P1

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

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.575

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.547

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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.519

Alfa AF: 0.530 Hom.: 5417

Bravo AF: 0.470

Asia WGS AF: 0.354 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	14
Dann	Benign	0.89

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