NM_007122.5:c.561-112T>G

Variant names:

• chr1-161040984-A-C
• rs2516841
• NM_007122.5:c.561-112T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007122.5(USF1):​c.561-112T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USF1 NM_007122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF1	NM_007122.5	c.561-112T>G		intron_variant	Intron 7 of 10	ENST00000368021.7	NP_009053.1
USF1	NM_001276373.2	c.561-112T>G		intron_variant	Intron 7 of 10		NP_001263302.1
USF1	NM_207005.3	c.384-112T>G		intron_variant	Intron 7 of 10		NP_996888.1
USF1	XM_047429959.1	c.384-112T>G		intron_variant	Intron 4 of 7		XP_047285915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF1	ENST00000368021.7	c.561-112T>G		intron_variant	Intron 7 of 10	1	NM_007122.5	ENSP00000357000.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1216900 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 606518

African (AFR) AF: 0.00 AC: 0 AN: 28544

American (AMR) AF: 0.00 AC: 0 AN: 34118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21572

East Asian (EAS) AF: 0.00 AC: 0 AN: 37198

South Asian (SAS) AF: 0.00 AC: 0 AN: 72218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4470

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 926878

Other (OTH) AF: 0.00 AC: 0 AN: 51844

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.35
PhyloP100		-0.54

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: rs2516841; hg19: chr1-161010774;