Variant 1-161041352-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007122.5(USF1):c.532A>G(p.Ile178Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,612,342 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 0.000013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

USF1
NM_007122.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

Variant links:

Genes affected

USF1 (HGNC:12593): (upstream transcription factor 1) This gene encodes a member of the basic helix-loop-helix leucine zipper family, and can function as a cellular transcription factor. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. This gene has been linked to familial combined hyperlipidemia (FCHL). Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been defined on chromosome 21. [provided by RefSeq, Feb 2013]

USF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22612411).

BS2

High AC in GnomAdExome at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USF1	NM_007122.5 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	7/11	ENST00000368021.7
USF1	NM_001276373.2 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	7/11
USF1	NM_207005.3 linkuse as main transcript	c.355A>G	p.Ile119Val	missense_variant	7/11
USF1	XM_047429959.1 linkuse as main transcript	c.355A>G	p.Ile119Val	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF1	ENST00000368021.7 linkuse as main transcript	c.532A>G	p.Ile178Val	missense_variant	7/11	1	NM_007122.5	P1	P22415-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000971

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251346

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461466

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73604

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000971

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.532A>G (p.I178V) alteration is located in exon 7 (coding exon 6) of the USF1 gene. This alteration results from a A to G substitution at nucleotide position 532, causing the isoleucine (I) at amino acid position 178 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T;.;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.042

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.6

M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.66

N;N;N;N

REVEL

Uncertain

0.42

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.28

T;T;T;.

Polyphen

0.72

P;P;.;.

Vest4

0.36

MutPred

0.16

Loss of catalytic residue at P180 (P = 0.0303);Loss of catalytic residue at P180 (P = 0.0303);.;.;

MVP

0.91

MPC

1.0

ClinPred

0.25

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over