dbSNP rs200773644: USF2:p.Glu29Asp (chr19-35269470-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003367.4(USF2):c.87G>T(p.Glu29Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,550,580 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00039 ( 1 hom. )

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.174

Publications

0 publications found

Variant links:

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]

USF2 links:

ENSG00000307673 (HGNC:):

ENSG00000307673 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14731047).

BS2

High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USF2	NM_003367.4	MANE Select	c.87G>T	p.Glu29Asp	missense	Exon 2 of 10	NP_003358.1	Q15853-1
USF2	NM_207291.3		c.87G>T	p.Glu29Asp	missense	Exon 2 of 9	NP_997174.1	Q15853-3
USF2	NM_001321150.2		c.87G>T	p.Glu29Asp	missense	Exon 2 of 8	NP_001308079.1	Q15853-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USF2	ENST00000222305.8	TSL:1 MANE Select	c.87G>T	p.Glu29Asp	missense	Exon 2 of 10	ENSP00000222305.2	Q15853-1
USF2	ENST00000343550.9	TSL:1	c.87G>T	p.Glu29Asp	missense	Exon 2 of 9	ENSP00000340633.4	Q15853-3
USF2	ENST00000379134.7	TSL:1	c.87G>T	p.Glu29Asp	missense	Exon 2 of 8	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes

AF:

0.000199

AC:

AN:

150742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000385

Gnomad OTH

AF:

0.000483

GnomAD2 exomes

AF:

0.000160

AC:

AN:

174692

AF XY:

0.000154

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000832

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000385

AC:

539

AN:

1399838

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

255

AN XY:

695108

show subpopulations

African (AFR)

AF:

0.000102

AC:

AN:

29346

American (AMR)

AF:

0.00

AC:

AN:

38884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24340

East Asian (EAS)

AF:

0.00

AC:

AN:

35204

South Asian (SAS)

AF:

0.00

AC:

AN:

79626

European-Finnish (FIN)

AF:

0.0000716

AC:

AN:

41924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4012

European-Non Finnish (NFE)

AF:

0.000478

AC:

521

AN:

1088872

Other (OTH)

AF:

0.000208

AC:

AN:

57630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000199

AC:

AN:

150742

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73592

show subpopulations

African (AFR)

AF:

0.0000730

AC:

AN:

41088

American (AMR)

AF:

0.00

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5024

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000385

AC:

AN:

67592

Other (OTH)

AF:

0.000483

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000227

ExAC

AF:

0.000139

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.0

PhyloP100

0.17

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.83

REVEL

Benign

0.14

Sift

Benign

0.26

Sift4G

Benign

0.37

Polyphen

0.0010

Vest4

0.14

MutPred

0.15

Loss of sheet (P = 0.0315)

MVP

0.31

MPC

0.74

ClinPred

0.035

GERP RS

0.73

PromoterAI

-0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.12

gMVP

0.077

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over