1-161040984-A-G

Variant names:

• chr1-161040984-A-G
• rs2516841
• NM_007122.5:c.561-112T>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.561-112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,366,500 control chromosomes in the GnomAD database, including 394,472 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 0.77 (45272 hom., cov: 30)
  • Exomes 𝑓: 0.76 (349200 hom.)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5	c.561-112T>C		intron_variant	Intron 7 of 10	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.561-112T>C		intron_variant	Intron 7 of 10		NP_001263302.1
USF1	NM_207005.3	c.384-112T>C		intron_variant	Intron 7 of 10		NP_996888.1
USF1	XM_047429959.1	c.384-112T>C		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.561-112T>C		intron_variant	Intron 7 of 10	1	NM_007122.5	ENSP00000357000.3

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117086 AN: 151892 Hom.: 45240 Cov.: 30

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.777

GnomAD4 exome AF: 0.757 AC: 919496 AN: 1214490 Hom.: 349200 AF XY: 0.756 AC XY: 457528 AN XY: 605372

African (AFR) AF: 0.809 AC: 23057 AN: 28510

American (AMR) AF: 0.788 AC: 26829 AN: 34066

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 16662 AN: 21520

East Asian (EAS) AF: 0.874 AC: 32490 AN: 37172

South Asian (SAS) AF: 0.717 AC: 51697 AN: 72140

European-Finnish (FIN) AF: 0.752 AC: 30067 AN: 40006

Middle Eastern (MID) AF: 0.778 AC: 3473 AN: 4462

European-Non Finnish (NFE) AF: 0.753 AC: 696175 AN: 924848

Other (OTH) AF: 0.754 AC: 39046 AN: 51766

GnomAD4 genome AF: 0.771 AC: 117172 AN: 152010 Hom.: 45272 Cov.: 30 AF XY: 0.770 AC XY: 57165 AN XY: 74272

African (AFR) AF: 0.809 AC: 33533 AN: 41472

American (AMR) AF: 0.748 AC: 11413 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2702 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4398 AN: 5164

South Asian (SAS) AF: 0.718 AC: 3458 AN: 4818

European-Finnish (FIN) AF: 0.765 AC: 8077 AN: 10562

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51011 AN: 67950

Other (OTH) AF: 0.779 AC: 1644 AN: 2110

Alfa AF: 0.761 Hom.: 9213

Bravo AF: 0.777

Asia WGS AF: 0.736 AC: 2561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.73
DANN	Benign	0.38
PhyloP100		-0.54
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: rs2516841; hg19: chr1-161010774;