1-161044859-A-G

Position:

• chr1-161044859-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007122.5(USF1):​c.-86+999T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,418 control chromosomes in the GnomAD database, including 8,566 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 0.28 (8558 hom., cov: 32)
  • Exomes 𝑓: 0.21 (8 hom.)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USF1	NM_007122.5	c.-86+999T>C		intron_variant		ENST00000368021.7
USF1	NM_001276373.2	c.-86+53T>C		intron_variant
USF1	NM_207005.3	c.-232+999T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF1	ENST00000368021.7	c.-86+999T>C		intron_variant		1	NM_007122.5	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42700 AN: 151950 Hom.: 8539 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.209 AC: 73 AN: 350 Hom.: 8 AF XY: 0.182 AC XY: 31 AN XY: 170

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.281 AC: 42763 AN: 152068 Hom.: 8558 Cov.: 32 AF XY: 0.282 AC XY: 20968 AN XY: 74334

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.258

Alfa AF: 0.178 Hom.: 1496

Bravo AF: 0.307

Asia WGS AF: 0.384 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.6
DANN	Benign	0.84

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: rs1556259; hg19: chr1-161014649;