rs2516838

Variant names:

• chr1-161044580-C-G
• rs2516838
• NM_007122.5:c.-85-1220G>C

Variant summary

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

The NM_007122.5(USF1):​c.-85-1220G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,018 control chromosomes in the GnomAD database, including 5,902 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 0.27 (5902 hom., cov: 31)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 17 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5	c.-85-1220G>C		intron_variant	Intron 1 of 10	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.-86+332G>C		intron_variant	Intron 1 of 10		NP_001263302.1
USF1	NM_207005.3	c.-231-1220G>C		intron_variant	Intron 1 of 10		NP_996888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.-85-1220G>C		intron_variant	Intron 1 of 10	1	NM_007122.5	ENSP00000357000.3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41199 AN: 151902 Hom.: 5898 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41222 AN: 152018 Hom.: 5902 Cov.: 31 AF XY: 0.268 AC XY: 19905 AN XY: 74286

African (AFR) AF: 0.192 AC: 7955 AN: 41482

American (AMR) AF: 0.224 AC: 3426 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3468

East Asian (EAS) AF: 0.146 AC: 756 AN: 5168

South Asian (SAS) AF: 0.301 AC: 1449 AN: 4810

European-Finnish (FIN) AF: 0.273 AC: 2878 AN: 10532

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.336 AC: 22815 AN: 67958

Other (OTH) AF: 0.280 AC: 591 AN: 2112

Alfa AF: 0.298 Hom.: 990

Bravo AF: 0.264

Asia WGS AF: 0.208 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.31
PromoterAI		0.014	Neutral
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: rs2516838; hg19: chr1-161014370;