NM_003112.5:c.1678+13949T>G

Variant names:

• chr7-21444792-T-G
• rs9639379
• NM_003112.5:c.1678+13949T>G

Variant summary

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

The NM_003112.5(SP4):​c.1678+13949T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,006 control chromosomes in the GnomAD database, including 30,201 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 0.63 (30201 hom., cov: 33)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 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.1678+13949T>G		intron	N/A	NP_003103.2
	SP4	NM_001326542.2		c.1627+13949T>G		intron	N/A	NP_001313471.1
	SP4	NM_001326543.2		c.739+13949T>G		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.1678+13949T>G		intron	N/A	ENSP00000222584.3
	SP4	ENST00000649633.1		c.1627+13949T>G		intron	N/A	ENSP00000496957.1
	SP4	ENST00000432066.2	TSL:5	c.7+16534T>G		intron	N/A	ENSP00000393623.2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95106 AN: 151888 Hom.: 30177 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.626 AC: 95167 AN: 152006 Hom.: 30201 Cov.: 33 AF XY: 0.623 AC XY: 46272 AN XY: 74272

African (AFR) AF: 0.644 AC: 26701 AN: 41460

American (AMR) AF: 0.460 AC: 7025 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2237 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2742 AN: 5166

South Asian (SAS) AF: 0.602 AC: 2904 AN: 4824

European-Finnish (FIN) AF: 0.666 AC: 7034 AN: 10556

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44363 AN: 67930

Other (OTH) AF: 0.631 AC: 1327 AN: 2104

Alfa AF: 0.638 Hom.: 7164

Bravo AF: 0.609

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9639379; hg19: chr7-21484410;