dbSNP rs555503800: USF2:p.Pro135Ser (chr19-35269977-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003367.4(USF2):c.403C>T(p.Pro135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,344,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.815

Publications

2 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034547657).

BS2

High AC in GnomAd4 at 44 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.403C>T	p.Pro135Ser	missense	Exon 4 of 10	NP_003358.1	Q15853-1
USF2	NM_207291.3		c.228+278C>T		intron	N/A	NP_997174.1	Q15853-3
USF2	NM_001321150.2		c.228+278C>T		intron	N/A	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.403C>T	p.Pro135Ser	missense	Exon 4 of 10	ENSP00000222305.2	Q15853-1
USF2	ENST00000343550.9	TSL:1	c.228+278C>T		intron	N/A	ENSP00000340633.4	Q15853-3
USF2	ENST00000379134.7	TSL:1	c.228+278C>T		intron	N/A	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000388

AC:

AN:

2580

AF XY:

0.000722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000812

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000515

AC:

614

AN:

1192546

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

296

AN XY:

574744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23512

American (AMR)

AF:

0.000404

AC:

AN:

9906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16460

East Asian (EAS)

AF:

0.00

AC:

AN:

27254

South Asian (SAS)

AF:

0.000527

AC:

AN:

47434

European-Finnish (FIN)

AF:

0.000321

AC:

AN:

28020

Middle Eastern (MID)

AF:

0.00210

AC:

AN:

3340

European-Non Finnish (NFE)

AF:

0.000544

AC:

537

AN:

987496

Other (OTH)

AF:

0.000651

AC:

AN:

49124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000289

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41570

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

67998

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000582

Hom.:

Bravo

AF:

0.000348

ExAC

AF:

0.000125

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

0.063

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.90

PhyloP100

-0.81

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.26

REVEL

Benign

0.25

Sift

Uncertain

0.025

Sift4G

Benign

0.74

Polyphen

0.035

Vest4

0.071

MutPred

0.19

Loss of catalytic residue at P132 (P = 0.0193)

MVP

0.30

MPC

0.82

ClinPred

0.040

GERP RS

1.3

PromoterAI

-0.00040

Neutral

(source)

Varity_R

0.10

gMVP

0.36

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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