rs12821290

Variant names:

• chr12-53416668-A-G
• rs12821290
• NM_138473.3:c.*5428A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_138473.3(SP1):​c.*5428A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 150,870 control chromosomes in the GnomAD database, including 98 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 0.029 (98 hom., cov: 31)
• Consequence: SP1 NM_138473.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 2 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=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0294 (4442/150870) while in subpopulation NFE AF = 0.0454 (3065/67524). AF 95% confidence interval is 0.0441. There are 98 homozygotes in GnomAd4. There are 2145 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4442 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP1	NM_138473.3	c.*5428A>G		downstream_gene_variant		ENST00000327443.9	NP_612482.2
SP1	NM_003109.1	c.*5428A>G		downstream_gene_variant			NP_003100.1
SP1	NM_001251825.2	c.*5428A>G		downstream_gene_variant			NP_001238754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP1	ENST00000327443.9	c.*5428A>G		downstream_gene_variant		1	NM_138473.3	ENSP00000329357.4
SP1	ENST00000426431.2	c.*5428A>G		downstream_gene_variant		1		ENSP00000404263.2

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4444 AN: 150752 Hom.: 98 Cov.: 31

Gnomad AFR AF: 0.00852

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0269

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0248

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

GnomAD4 genome AF: 0.0294 AC: 4442 AN: 150870 Hom.: 98 Cov.: 31 AF XY: 0.0291 AC XY: 2145 AN XY: 73730

African (AFR) AF: 0.00850 AC: 349 AN: 41068

American (AMR) AF: 0.0221 AC: 333 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.0269 AC: 93 AN: 3458

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.0242 AC: 115 AN: 4748

European-Finnish (FIN) AF: 0.0384 AC: 405 AN: 10538

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.0454 AC: 3065 AN: 67524

Other (OTH) AF: 0.0245 AC: 51 AN: 2082

Alfa AF: 0.0397 Hom.: 303

Bravo AF: 0.0267

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.033
DANN	Benign	0.28
PhyloP100		-2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12821290; hg19: chr12-53810452;