rs12668354

Variant names:

• chr7-21492273-C-A
• rs12668354
• NM_003112.5:c.2107+10150C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21492273-C-A
• chr7-21492273-C-G
• chr7-21492273-C-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.2107+10150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,158 control chromosomes in the GnomAD database, including 45,255 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 0.77 (45255 hom., cov: 33)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003112.5. 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
	SP4	NM_003112.5	MANE Select	c.2107+10150C>A		intron	N/A	NP_003103.2	Q02446
	SP4	NM_001326542.2		c.2056+10150C>A		intron	N/A	NP_001313471.1	A0A3B3IRW4
	SP4	NM_001326543.2		c.1168+10150C>A		intron	N/A	NP_001313472.1	Q32M51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	ENST00000222584.8	TSL:1 MANE Select	c.2107+10150C>A		intron	N/A	ENSP00000222584.3	Q02446
	SP4	ENST00000959244.1		c.2098+10150C>A		intron	N/A	ENSP00000629303.1
	SP4	ENST00000649633.1		c.2056+10150C>A		intron	N/A	ENSP00000496957.1	A0A3B3IRW4

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116466 AN: 152040 Hom.: 45195 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.766 AC: 116584 AN: 152158 Hom.: 45255 Cov.: 33 AF XY: 0.770 AC XY: 57236 AN XY: 74366

African (AFR) AF: 0.899 AC: 37358 AN: 41560

American (AMR) AF: 0.732 AC: 11176 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2484 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4648 AN: 5168

South Asian (SAS) AF: 0.767 AC: 3695 AN: 4820

European-Finnish (FIN) AF: 0.713 AC: 7532 AN: 10568

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47281 AN: 67976

Other (OTH) AF: 0.741 AC: 1565 AN: 2112

Alfa AF: 0.714 Hom.: 19542

Bravo AF: 0.771

Asia WGS AF: 0.812 AC: 2818 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.15
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: rs12668354; hg19: chr7-21531891;