rs2073658

Variant names:

• chr1-161040972-C-A
• rs2073658
• NM_007122.5:c.561-100G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-161040972-C-A
• chr1-161040972-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007122.5(USF1):​c.561-100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,317,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5	c.561-100G>T		intron_variant	Intron 7 of 10	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.561-100G>T		intron_variant	Intron 7 of 10		NP_001263302.1
USF1	NM_207005.3	c.384-100G>T		intron_variant	Intron 7 of 10		NP_996888.1
USF1	XM_047429959.1	c.384-100G>T		intron_variant	Intron 4 of 7		XP_047285915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.561-100G>T		intron_variant	Intron 7 of 10	1	NM_007122.5	ENSP00000357000.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1317290 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 655664

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30692

American (AMR) AF: 0.00 AC: 0 AN: 37616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23170

East Asian (EAS) AF: 0.00 AC: 0 AN: 38428

South Asian (SAS) AF: 0.00 AC: 0 AN: 77468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5078

European-Non Finnish (NFE) AF: 9.95e-7 AC: 1 AN: 1005194

Other (OTH) AF: 0.00 AC: 0 AN: 55472

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.70
PhyloP100		1.5

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

Other links and lift over

dbSNP: rs2073658; hg19: chr1-161010762;