NM_003112.5:c.2108-749T>A

Variant names:

• chr7-21510273-T-A
• rs1018954
• NM_003112.5:c.2108-749T>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.2108-749T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,076 control chromosomes in the GnomAD database, including 12,102 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 0.39 (12102 hom., cov: 32)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP4	NM_003112.5	c.2108-749T>A		intron_variant	Intron 5 of 5	ENST00000222584.8	NP_003103.2
SP4	NM_001326542.2	c.2057-749T>A		intron_variant	Intron 5 of 5		NP_001313471.1
SP4	NM_001326543.2	c.1169-749T>A		intron_variant	Intron 5 of 5		NP_001313472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.2108-749T>A		intron_variant	Intron 5 of 5	1	NM_003112.5	ENSP00000222584.3
SP4	ENST00000649633.1	c.2057-749T>A		intron_variant	Intron 5 of 5			ENSP00000496957.1
SP4	ENST00000448246.1	n.*403-749T>A		intron_variant	Intron 4 of 4	5		ENSP00000390817.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58704 AN: 151956 Hom.: 12083 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.386 AC: 58764 AN: 152076 Hom.: 12102 Cov.: 32 AF XY: 0.381 AC XY: 28342 AN XY: 74352

African (AFR) AF: 0.349 AC: 14484 AN: 41496

American (AMR) AF: 0.292 AC: 4463 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1521 AN: 3464

East Asian (EAS) AF: 0.0615 AC: 318 AN: 5168

South Asian (SAS) AF: 0.205 AC: 986 AN: 4812

European-Finnish (FIN) AF: 0.500 AC: 5288 AN: 10570

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30339 AN: 67978

Other (OTH) AF: 0.375 AC: 790 AN: 2104

Alfa AF: 0.437 Hom.: 2187

Bravo AF: 0.367

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.94
DANN	Benign	0.64
PhyloP100		-0.12
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: rs1018954; hg19: chr7-21549891;