12-53389175-G-A

Variant names:

• chr12-53389175-G-A
• rs12368491
• NM_138473.3:c.1675+5553G>A

Variant summary

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

The NM_138473.3(SP1):​c.1675+5553G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 146,232 control chromosomes in the GnomAD database, including 2,511 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 (2511 hom., cov: 29)
• Consequence: SP1 NM_138473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138473.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP1	NM_138473.3	MANE Select	c.1675+5553G>A		intron	N/A	NP_612482.2
	SP1	NM_003109.1		c.1654+5553G>A		intron	N/A	NP_003100.1	P08047-2
	SP1	NM_001251825.2		c.1531+5553G>A		intron	N/A	NP_001238754.1	P08047-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP1	ENST00000327443.9	TSL:1 MANE Select	c.1675+5553G>A		intron	N/A	ENSP00000329357.4	P08047-1
	SP1	ENST00000426431.2	TSL:1	c.1654+5553G>A		intron	N/A	ENSP00000404263.2	P08047-2
	SP1	ENST00000854917.1		c.271+6957G>A		intron	N/A	ENSP00000524976.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 26820 AN: 146148 Hom.: 2507 Cov.: 29

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0856

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.184 AC: 26835 AN: 146232 Hom.: 2511 Cov.: 29 AF XY: 0.182 AC XY: 12916 AN XY: 70890

African (AFR) AF: 0.211 AC: 8320 AN: 39406

American (AMR) AF: 0.200 AC: 2903 AN: 14514

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 405 AN: 3412

East Asian (EAS) AF: 0.200 AC: 988 AN: 4946

South Asian (SAS) AF: 0.151 AC: 707 AN: 4672

European-Finnish (FIN) AF: 0.153 AC: 1423 AN: 9326

Middle Eastern (MID) AF: 0.0882 AC: 24 AN: 272

European-Non Finnish (NFE) AF: 0.174 AC: 11598 AN: 66772

Other (OTH) AF: 0.157 AC: 319 AN: 2030

Alfa AF: 0.169 Hom.: 284

Bravo AF: 0.184

Asia WGS AF: 0.150 AC: 520 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.44
PhyloP100		-0.043
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: rs12368491; hg19: chr12-53782959;