Genetic Variant USF2:p.Arg125His (chr19-35269948-G-A) – 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.374G>A(p.Arg125His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000596 in 1,343,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000059 ( 0 hom. )

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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:

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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=0.13916218).

BS2

High AC in GnomAdExome4 at 7 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.374G>A	p.Arg125His	missense	Exon 4 of 10	NP_003358.1	Q15853-1
USF2	NM_207291.3		c.228+249G>A		intron	N/A	NP_997174.1	Q15853-3
USF2	NM_001321150.2		c.228+249G>A		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.374G>A	p.Arg125His	missense	Exon 4 of 10	ENSP00000222305.2	Q15853-1
USF2	ENST00000343550.9	TSL:1	c.228+249G>A		intron	N/A	ENSP00000340633.4	Q15853-3
USF2	ENST00000379134.7	TSL:1	c.228+249G>A		intron	N/A	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

2384

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000588

AC:

AN:

1190930

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

573754

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23464

American (AMR)

AF:

0.00

AC:

AN:

9852

Ashkenazi Jewish (ASJ)

AF:

0.000183

AC:

AN:

16396

East Asian (EAS)

AF:

0.00

AC:

AN:

27218

South Asian (SAS)

AF:

0.00

AC:

AN:

47092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3374

European-Non Finnish (NFE)

AF:

0.00000406

AC:

AN:

986086

Other (OTH)

AF:

0.00

AC:

AN:

49048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.12

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.065

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.0

PhyloP100

1.2

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.19

REVEL

Benign

0.18

Sift

Benign

0.042

Sift4G

Benign

0.13

Polyphen

0.88

Vest4

0.14

MutPred

0.23

Loss of methylation at R123 (P = 0.0179)

MVP

0.26

MPC

1.1

ClinPred

0.33

GERP RS

1.2

PromoterAI

-0.0072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.063

gMVP

0.26

Mutation Taster

=95/5

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over