rs12368491

Positions:

• chr12-53389175-G-A
• chr12-53389175-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP1	NM_138473.3	c.1675+5553G>A		intron_variant		ENST00000327443.9	NP_612482.2
SP1	NM_003109.1	c.1654+5553G>A		intron_variant			NP_003100.1
SP1	NM_001251825.2	c.1531+5553G>A		intron_variant			NP_001238754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP1	ENST00000327443.9	c.1675+5553G>A		intron_variant		1	NM_138473.3	ENSP00000329357.4
SP1	ENST00000426431.2	c.1654+5553G>A		intron_variant		1		ENSP00000404263.2

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

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.157

Alfa AF: 0.166 Hom.: 259

Bravo AF: 0.184

Asia WGS AF: 0.150 AC: 520 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs12368491; hg19: chr12-53782959;