rs10405246

Variant names:

• chr19-35278046-A-G
• rs10405246
• NM_003367.4:c.728-652A>G

Variant summary

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

The NM_003367.4(USF2):​c.728-652A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,184 control chromosomes in the GnomAD database, including 3,486 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 0.21 (3483 hom., cov: 33)
  • Exomes 𝑓: 0.24 (3 hom.)
• Consequence: USF2 NM_003367.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF2	NM_003367.4	c.728-652A>G		intron_variant	Intron 7 of 9	ENST00000222305.8	NP_003358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF2	ENST00000222305.8	c.728-652A>G		intron_variant	Intron 7 of 9	1	NM_003367.4	ENSP00000222305.2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31659 AN: 151996 Hom.: 3488 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.243 AC: 17 AN: 70 Hom.: 3 Cov.: 0 AF XY: 0.263 AC XY: 10 AN XY: 38

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.333 AC: 4 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.240 AC: 12 AN: 50

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.208 AC: 31661 AN: 152114 Hom.: 3483 Cov.: 33 AF XY: 0.208 AC XY: 15494 AN XY: 74370

African (AFR) AF: 0.185 AC: 7689 AN: 41474

American (AMR) AF: 0.172 AC: 2629 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3470

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5188

South Asian (SAS) AF: 0.216 AC: 1039 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2824 AN: 10580

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15921 AN: 67974

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.220 Hom.: 15059

Bravo AF: 0.196

Asia WGS AF: 0.135 AC: 468 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	6.0
DANN	Benign	0.57
PhyloP100		0.099
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: rs10405246; hg19: chr19-35768949;