rs916145

Positions:

• chr19-35276981-C-G
• chr19-35276981-C-T

Variant summary

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

The NM_003367.4(USF2):​c.728-1717C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,358 control chromosomes in the GnomAD database, including 61,244 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 0.89 (61208 hom., cov: 33)
  • Exomes 𝑓: 0.93 (36 hom.)
• Consequence: USF2 NM_003367.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

USF2 (HGNC:12594): (upstream transcription factor 2, c-fos interacting) This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USF2	NM_003367.4	c.728-1717C>G		intron_variant		ENST00000222305.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF2	ENST00000222305.8	c.728-1717C>G		intron_variant		1	NM_003367.4	P3

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136123 AN: 152156 Hom.: 61144 Cov.: 33

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.907

GnomAD4 exome AF: 0.929 AC: 78 AN: 84 Hom.: 36 Cov.: 0 AF XY: 0.939 AC XY: 62 AN XY: 66

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.895 AC: 136248 AN: 152274 Hom.: 61208 Cov.: 33 AF XY: 0.894 AC XY: 66577 AN XY: 74448

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.906

Alfa AF: 0.878 Hom.: 2801

Bravo AF: 0.898

Asia WGS AF: 0.801 AC: 2788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs916145; hg19: chr19-35767884;