chr1-161042970-T-C

Variant names:

• chr1-161042970-T-C
• rs2073653
• NM_007122.5:c.9-88A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007122.5(USF1):​c.9-88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,569,120 control chromosomes in the GnomAD database, including 38,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (8633 hom., cov: 32)
  • Exomes 𝑓: 0.18 (30299 hom.)
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.54
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	NM_007122.5	MANE Select	c.9-88A>G		intron	N/A	NP_009053.1	P22415-1
	USF1	NM_001276373.2		c.9-88A>G		intron	N/A	NP_001263302.1	A0A0S2Z4U5
	USF1	NM_207005.3		c.-138-88A>G		intron	N/A	NP_996888.1	P22415-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF1	ENST00000368021.7	TSL:1 MANE Select	c.9-88A>G		intron	N/A	ENSP00000357000.3	P22415-1
	USF1	ENST00000368020.5	TSL:1	c.9-88A>G		intron	N/A	ENSP00000356999.1	P22415-1
	USF1	ENST00000961613.1		c.9-88A>G		intron	N/A	ENSP00000631672.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42878 AN: 152002 Hom.: 8614 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.177 AC: 251344 AN: 1417000 Hom.: 30299 AF XY: 0.178 AC XY: 126017 AN XY: 707394

African (AFR) AF: 0.567 AC: 18509 AN: 32666

American (AMR) AF: 0.367 AC: 16359 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5098 AN: 25860

East Asian (EAS) AF: 0.547 AC: 21577 AN: 39454

South Asian (SAS) AF: 0.255 AC: 21733 AN: 85216

European-Finnish (FIN) AF: 0.143 AC: 7617 AN: 53202

Middle Eastern (MID) AF: 0.235 AC: 1337 AN: 5682

European-Non Finnish (NFE) AF: 0.137 AC: 146849 AN: 1071450

Other (OTH) AF: 0.208 AC: 12265 AN: 58932

GnomAD4 genome AF: 0.282 AC: 42942 AN: 152120 Hom.: 8633 Cov.: 32 AF XY: 0.283 AC XY: 21049 AN XY: 74360

African (AFR) AF: 0.550 AC: 22818 AN: 41464

American (AMR) AF: 0.273 AC: 4172 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3466

East Asian (EAS) AF: 0.522 AC: 2705 AN: 5182

South Asian (SAS) AF: 0.247 AC: 1189 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1446 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9252 AN: 67998

Other (OTH) AF: 0.259 AC: 548 AN: 2116

Alfa AF: 0.190 Hom.: 14848

Bravo AF: 0.308

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0040
DANN	Benign	0.73
PhyloP100		-5.5
PromoterAI		-0.022	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: rs2073653; hg19: chr1-161012760; COSMIC: COSV57036561; COSMIC: COSV57036561;