NM_003112.5:c.1679-12270A>G

Variant names:

• chr7-21464809-A-G
• rs17144465
• NM_003112.5:c.1679-12270A>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.1679-12270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,136 control chromosomes in the GnomAD database, including 3,186 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 0.15 (3186 hom., cov: 32)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP4	NM_003112.5	c.1679-12270A>G		intron_variant	Intron 3 of 5	ENST00000222584.8	NP_003103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.1679-12270A>G		intron_variant	Intron 3 of 5	1	NM_003112.5	ENSP00000222584.3
SP4	ENST00000649633.1	c.1628-12270A>G		intron_variant	Intron 3 of 5			ENSP00000496957.1
SP4	ENST00000432066.2	c.8-12270A>G		intron_variant	Intron 1 of 1	5		ENSP00000393623.2
SP4	ENST00000448246.1	n.124-12270A>G		intron_variant	Intron 2 of 4	5		ENSP00000390817.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22622 AN: 152018 Hom.: 3173 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.149 AC: 22676 AN: 152136 Hom.: 3186 Cov.: 32 AF XY: 0.157 AC XY: 11700 AN XY: 74380

African (AFR) AF: 0.235 AC: 9744 AN: 41498

American (AMR) AF: 0.280 AC: 4282 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3468

East Asian (EAS) AF: 0.623 AC: 3213 AN: 5156

South Asian (SAS) AF: 0.200 AC: 961 AN: 4814

European-Finnish (FIN) AF: 0.0699 AC: 741 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3227 AN: 68010

Other (OTH) AF: 0.119 AC: 251 AN: 2108

Alfa AF: 0.0890 Hom.: 5456

Bravo AF: 0.170

Asia WGS AF: 0.412 AC: 1431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.6
DANN	Benign	0.73
PhyloP100		0.94
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: rs17144465; hg19: chr7-21504427;