rs2282888

chr7-21436514-G-Achr7-21436514-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003112.5(SP4):c.1678+5671G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,142 control chromosomes in the GnomAD database, including 40,604 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 0.72 (40604 hom., cov: 32)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP4	NM_003112.5	c.1678+5671G>A		intron_variant		ENST00000222584.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP4	ENST00000222584.8	c.1678+5671G>A		intron_variant		1	NM_003112.5	P1
SP4	ENST00000432066.2	c.7+8256G>A		intron_variant		5
SP4	ENST00000649633.1	c.1627+5671G>A		intron_variant
SP4	ENST00000448246.1	c.123+7722G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109664 AN: 152022 Hom.: 40547 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.722 AC: 109781 AN: 152142 Hom.: 40604 Cov.: 32 AF XY: 0.724 AC XY: 53848 AN XY: 74374

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.692

Alfa AF: 0.643 Hom.: 39842

Bravo AF: 0.733

Asia WGS AF: 0.799 AC: 2779 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	0.023
Dann	Benign	0.62

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: rs2282888; hg19: chr7-21476132;