chr1-161042800-G-A

Variant names:

• chr1-161042800-G-A
• rs2073655
• NM_007122.5:c.58+33C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.79).
• 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 rank	MANE	Protein	UniProt
USF1	NM_007122.5	c.58+33C>T		intron_variant	Intron 3 of 10	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.58+33C>T		intron_variant	Intron 3 of 10		NP_001263302.1
USF1	NM_207005.3	c.-89+33C>T		intron_variant	Intron 3 of 10		NP_996888.1
USF1	XM_047429959.1	c.-218C>T		upstream_gene_variant			XP_047285915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.58+33C>T		intron_variant	Intron 3 of 10	1	NM_007122.5	ENSP00000357000.3

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

GnomAD2 exomes AF: 0.250 AC: 62800 AN: 251476 AF XY: 0.250

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 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

African (AFR) AF: 0.0600 AC: 2007 AN: 33476

American (AMR) AF: 0.256 AC: 11433 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7751 AN: 26132

East Asian (EAS) AF: 0.200 AC: 7946 AN: 39700

South Asian (SAS) AF: 0.169 AC: 14553 AN: 86252

European-Finnish (FIN) AF: 0.351 AC: 18766 AN: 53420

Middle Eastern (MID) AF: 0.252 AC: 1454 AN: 5766

European-Non Finnish (NFE) AF: 0.273 AC: 304029 AN: 1111680

Other (OTH) AF: 0.247 AC: 14923 AN: 60382

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

African (AFR) AF: 0.0653 AC: 2712 AN: 41556

American (AMR) AF: 0.249 AC: 3807 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1060 AN: 3468

East Asian (EAS) AF: 0.183 AC: 948 AN: 5172

South Asian (SAS) AF: 0.174 AC: 839 AN: 4828

European-Finnish (FIN) AF: 0.352 AC: 3728 AN: 10582

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18978 AN: 67984

Other (OTH) AF: 0.240 AC: 506 AN: 2112

Alfa AF: 0.248 Hom.: 1282

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
PhyloP100		1.3
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: rs2073655; hg19: chr1-161012590; COSMIC: COSV57037849; COSMIC: COSV57037849;