1-161042970-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5	c.9-88A>G		intron_variant	Intron 2 of 10	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.9-88A>G		intron_variant	Intron 2 of 10		NP_001263302.1
USF1	NM_207005.3	c.-138-88A>G		intron_variant	Intron 2 of 10		NP_996888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.9-88A>G		intron_variant	Intron 2 of 10	1	NM_007122.5	ENSP00000357000.3

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

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.208

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

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.259

Alfa AF: 0.168 Hom.: 4520

Bravo AF: 0.308

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0040
DANN	Benign	0.73

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: rs2073653; hg19: chr1-161012760; COSMIC: COSV57036561; COSMIC: COSV57036561;