1-161041527-A-G

Variant names:

• chr1-161041527-A-G
• rs2516840
• NM_007122.5:c.473-116T>C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.825

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.754

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.724

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

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.753

Alfa AF: 0.737 Hom.: 8733

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2516840; hg19: chr1-161011317;