rs7300593

Variant names:

• chr12-53396666-T-C
• rs7300593
• NM_138473.3:c.1676-9919T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138473.3(SP1):​c.1676-9919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,218 control chromosomes in the GnomAD database, including 2,652 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 (2652 hom., cov: 32)
• Consequence: SP1 NM_138473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• 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 rank	MANE	Protein	UniProt
SP1	NM_138473.3	c.1676-9919T>C		intron_variant	Intron 3 of 5	ENST00000327443.9	NP_612482.2
SP1	NM_003109.1	c.1655-9919T>C		intron_variant	Intron 3 of 5		NP_003100.1
SP1	NM_001251825.2	c.1532-9919T>C		intron_variant	Intron 3 of 5		NP_001238754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP1	ENST00000327443.9	c.1676-9919T>C		intron_variant	Intron 3 of 5	1	NM_138473.3	ENSP00000329357.4
SP1	ENST00000426431.2	c.1655-9919T>C		intron_variant	Intron 3 of 5	1		ENSP00000404263.2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27764 AN: 152100 Hom.: 2648 Cov.: 32

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: 0.149

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27780 AN: 152218 Hom.: 2652 Cov.: 32 AF XY: 0.181 AC XY: 13492 AN XY: 74400

African (AFR) AF: 0.209 AC: 8694 AN: 41540

American (AMR) AF: 0.203 AC: 3095 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1023 AN: 5178

South Asian (SAS) AF: 0.149 AC: 722 AN: 4830

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11685 AN: 68012

Other (OTH) AF: 0.154 AC: 325 AN: 2112

Alfa AF: 0.173 Hom.: 1180

Bravo AF: 0.184

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7300593; hg19: chr12-53790450;