chr1-161040972-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	NM_007122.5	MANE Select	c.561-100G>A		intron	N/A	NP_009053.1
	USF1	NM_001276373.2		c.561-100G>A		intron	N/A	NP_001263302.1
	USF1	NM_207005.3		c.384-100G>A		intron	N/A	NP_996888.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	ENST00000368021.7	TSL:1 MANE Select	c.561-100G>A		intron	N/A	ENSP00000357000.3
	USF1	ENST00000368020.5	TSL:1	c.561-100G>A		intron	N/A	ENSP00000356999.1
	USF1	ENST00000368019.5	TSL:5	c.477-100G>A		intron	N/A	ENSP00000356998.1

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

African (AFR) AF: 0.0598 AC: 1834 AN: 30680

American (AMR) AF: 0.254 AC: 9537 AN: 37516

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 6874 AN: 23130

East Asian (EAS) AF: 0.201 AC: 7711 AN: 38400

South Asian (SAS) AF: 0.137 AC: 10625 AN: 77406

European-Finnish (FIN) AF: 0.350 AC: 15442 AN: 44102

Middle Eastern (MID) AF: 0.253 AC: 1282 AN: 5066

European-Non Finnish (NFE) AF: 0.273 AC: 274220 AN: 1003264

Other (OTH) AF: 0.244 AC: 13495 AN: 55366

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

African (AFR) AF: 0.0652 AC: 2703 AN: 41484

American (AMR) AF: 0.249 AC: 3798 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1058 AN: 3460

East Asian (EAS) AF: 0.184 AC: 952 AN: 5172

South Asian (SAS) AF: 0.145 AC: 700 AN: 4818

European-Finnish (FIN) AF: 0.352 AC: 3710 AN: 10546

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18938 AN: 67934

Other (OTH) AF: 0.239 AC: 505 AN: 2110

Alfa AF: 0.243 Hom.: 6758

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

Sep 01, 2005

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.68
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV107321929; COSMIC: COSV107321929;