Variant 12-53383387-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_138473.3(SP1):c.1440A>G(p.Gln480=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,614,024 control chromosomes in the GnomAD database, including 24,865 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 0.18 ( 2647 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22218 hom. )

Consequence

SP1
NM_138473.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Variant links:

Genes affected

SP1 (HGNC:11205): (Sp1 transcription factor) The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

SP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=2.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SP1	NM_138473.3 linkuse as main transcript	c.1440A>G	p.Gln480=	synonymous_variant	3/6	ENST00000327443.9
SP1	NM_003109.1 linkuse as main transcript	c.1419A>G	p.Gln473=	synonymous_variant	3/6
SP1	NM_001251825.2 linkuse as main transcript	c.1296A>G	p.Gln432=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP1	ENST00000327443.9 linkuse as main transcript	c.1440A>G	p.Gln480=	synonymous_variant	3/6	1	NM_138473.3	P4	P08047-1
SP1	ENST00000426431.2 linkuse as main transcript	c.1419A>G	p.Gln473=	synonymous_variant	3/6	1		A1	P08047-2

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27766

AN:

152040

Hom.:

2643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.173

AC:

43625

AN:

251460

Hom.:

3864

AF XY:

0.171

AC XY:

23214

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.172

AC:

251761

AN:

1461866

Hom.:

22218

Cov.:

AF XY:

0.171

AC XY:

124190

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.183

AC:

27782

AN:

152158

Hom.:

2647

Cov.:

AF XY:

0.182

AC XY:

13501

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.173

Hom.:

1770

Bravo

AF:

0.184

Asia WGS

AF:

0.150

AC:

521

AN:

3478

EpiCase

AF:

0.166

EpiControl

AF:

0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over