rs12673091

Variant names:

• chr7-21498449-A-G
• rs12673091
• NM_003112.5:c.2108-12573A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-21498449-A-G
• chr7-21498449-A-T

Variant summary

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

The NM_003112.5(SP4):​c.2108-12573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,994 control chromosomes in the GnomAD database, including 11,654 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 0.37 (11654 hom., cov: 31)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 7 publications found

Genes affected

SP4 (HGNC:11209): (Sp4 transcription factor) The protein encoded by this gene is a transcription factor that can bind to the GC promoter region of a variety of genes, including those of the photoreceptor signal transduction system. The encoded protein binds to the same sites in promoter CpG islands as does the transcription factor SP1, although its expression is much more restricted compared to that of SP1. This gene may be involved in bipolar disorder and schizophrenia. [provided by RefSeq, May 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP4	NM_003112.5	c.2108-12573A>G		intron_variant	Intron 5 of 5	ENST00000222584.8	NP_003103.2
SP4	NM_001326542.2	c.2057-12573A>G		intron_variant	Intron 5 of 5		NP_001313471.1
SP4	NM_001326543.2	c.1169-12573A>G		intron_variant	Intron 5 of 5		NP_001313472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.2108-12573A>G		intron_variant	Intron 5 of 5	1	NM_003112.5	ENSP00000222584.3
SP4	ENST00000649633.1	c.2057-12573A>G		intron_variant	Intron 5 of 5			ENSP00000496957.1
SP4	ENST00000448246.1	n.*403-12573A>G		intron_variant	Intron 4 of 4	5		ENSP00000390817.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56121 AN: 151876 Hom.: 11633 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.370 AC: 56181 AN: 151994 Hom.: 11654 Cov.: 31 AF XY: 0.379 AC XY: 28180 AN XY: 74282

African (AFR) AF: 0.440 AC: 18219 AN: 41450

American (AMR) AF: 0.444 AC: 6770 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3470

East Asian (EAS) AF: 0.840 AC: 4333 AN: 5160

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4820

European-Finnish (FIN) AF: 0.263 AC: 2780 AN: 10570

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19029 AN: 67968

Other (OTH) AF: 0.364 AC: 768 AN: 2108

Alfa AF: 0.328 Hom.: 2121

Bravo AF: 0.386

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		0.16
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: rs12673091; hg19: chr7-21538067;