rs3737787

Positions:

• chr1-161039733-G-A

Variant summary

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

The NM_007122.5(USF1):​c.*187C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 626,724 control chromosomes in the GnomAD database, including 20,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (4277 hom., cov: 32)
  • Exomes 𝑓: 0.26 (16626 hom.)
• Consequence: USF1 NM_007122.5 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -3.21

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF1	NM_007122.5	c.*187C>T		3_prime_UTR_variant	11/11	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.*187C>T		3_prime_UTR_variant	11/11		NP_001263302.1
USF1	NM_207005.3	c.*187C>T		3_prime_UTR_variant	11/11		NP_996888.1
USF1	XM_047429959.1	c.*187C>T		3_prime_UTR_variant	8/8		XP_047285915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.*187C>T		3_prime_UTR_variant	11/11	1	NM_007122.5	ENSP00000357000	P1
USF1	ENST00000368020.5	c.*187C>T		3_prime_UTR_variant	11/11	1		ENSP00000356999	P1
USF1	ENST00000472217.1	n.659C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32677 AN: 152038 Hom.: 4274 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.256 AC: 121703 AN: 474568 Hom.: 16626 Cov.: 5 AF XY: 0.251 AC XY: 62833 AN XY: 250274

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.215 AC: 32677 AN: 152156 Hom.: 4277 Cov.: 32 AF XY: 0.215 AC XY: 16011 AN XY: 74376

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.240

Alfa AF: 0.268 Hom.: 10656

Bravo AF: 0.205

Asia WGS AF: 0.133 AC: 469 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hyperlipidemia, familial combined, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3737787; hg19: chr1-161009523;