1-161041527-A-G

Variant names:

• chr1-161041527-A-G
• rs2516840
• NM_007122.5:c.473-116T>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.473-116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,469,900 control chromosomes in the GnomAD database, including 392,853 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 0.75 (43309 hom., cov: 30)
  • Exomes 𝑓: 0.73 (349544 hom.)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5	c.473-116T>C		intron_variant	Intron 6 of 10	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.473-116T>C		intron_variant	Intron 6 of 10		NP_001263302.1
USF1	NM_207005.3	c.296-116T>C		intron_variant	Intron 6 of 10		NP_996888.1
USF1	XM_047429959.1	c.296-116T>C		intron_variant	Intron 3 of 7		XP_047285915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.473-116T>C		intron_variant	Intron 6 of 10	1	NM_007122.5	ENSP00000357000.3

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114290 AN: 151836 Hom.: 43272 Cov.: 30

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.727 AC: 958073 AN: 1317946 Hom.: 349544 Cov.: 20 AF XY: 0.726 AC XY: 472841 AN XY: 651220

African (AFR) AF: 0.825 AC: 25005 AN: 30316

American (AMR) AF: 0.767 AC: 26410 AN: 34436

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 16253 AN: 22130

East Asian (EAS) AF: 0.875 AC: 32996 AN: 37704

South Asian (SAS) AF: 0.696 AC: 52569 AN: 75556

European-Finnish (FIN) AF: 0.754 AC: 37848 AN: 50200

Middle Eastern (MID) AF: 0.741 AC: 2870 AN: 3874

European-Non Finnish (NFE) AF: 0.718 AC: 724333 AN: 1008794

Other (OTH) AF: 0.724 AC: 39789 AN: 54936

GnomAD4 genome AF: 0.753 AC: 114381 AN: 151954 Hom.: 43309 Cov.: 30 AF XY: 0.753 AC XY: 55902 AN XY: 74242

African (AFR) AF: 0.824 AC: 34112 AN: 41418

American (AMR) AF: 0.713 AC: 10877 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2580 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4407 AN: 5168

South Asian (SAS) AF: 0.705 AC: 3388 AN: 4806

European-Finnish (FIN) AF: 0.763 AC: 8073 AN: 10576

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48481 AN: 67946

Other (OTH) AF: 0.753 AC: 1585 AN: 2104

Alfa AF: 0.739 Hom.: 8999

Bravo AF: 0.758

Asia WGS AF: 0.744 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.44
PhyloP100		-0.32
PromoterAI		-0.017	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: rs2516840; hg19: chr1-161011317;