NM_003112.5:c.1908-309G>A

Variant names:

• chr7-21481615-G-A
• rs10276352
• NM_003112.5:c.1908-309G>A

Variant summary

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

The NM_003112.5(SP4):​c.1908-309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,978 control chromosomes in the GnomAD database, including 20,615 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 0.51 (20615 hom., cov: 32)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	NM_003112.5	MANE Select	c.1908-309G>A		intron	N/A	NP_003103.2
	SP4	NM_001326542.2		c.1857-309G>A		intron	N/A	NP_001313471.1
	SP4	NM_001326543.2		c.969-309G>A		intron	N/A	NP_001313472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	ENST00000222584.8	TSL:1 MANE Select	c.1908-309G>A		intron	N/A	ENSP00000222584.3
	SP4	ENST00000649633.1		c.1857-309G>A		intron	N/A	ENSP00000496957.1
	SP4	ENST00000448246.1	TSL:5	n.*203-309G>A		intron	N/A	ENSP00000390817.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78122 AN: 151860 Hom.: 20599 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.514 AC: 78168 AN: 151978 Hom.: 20615 Cov.: 32 AF XY: 0.509 AC XY: 37818 AN XY: 74264

African (AFR) AF: 0.475 AC: 19690 AN: 41446

American (AMR) AF: 0.393 AC: 6003 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3466

East Asian (EAS) AF: 0.272 AC: 1405 AN: 5168

South Asian (SAS) AF: 0.493 AC: 2373 AN: 4818

European-Finnish (FIN) AF: 0.546 AC: 5759 AN: 10556

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39012 AN: 67940

Other (OTH) AF: 0.532 AC: 1122 AN: 2108

Alfa AF: 0.557 Hom.: 13171

Bravo AF: 0.498

Asia WGS AF: 0.357 AC: 1241 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.75
PhyloP100		0.090
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: rs10276352; hg19: chr7-21521233;