rs1018954

Positions:

• chr7-21510273-T-A
• chr7-21510273-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
SP4	NM_003112.5	c.2108-749T>A		intron_variant		ENST00000222584.8	NP_003103.2
SP4	NM_001326542.2	c.2057-749T>A		intron_variant			NP_001313471.1
SP4	NM_001326543.2	c.1169-749T>A		intron_variant			NP_001313472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.2108-749T>A		intron_variant		1	NM_003112.5	ENSP00000222584	P1
SP4	ENST00000649633.1	c.2057-749T>A		intron_variant				ENSP00000496957
SP4	ENST00000448246.1	c.*403-749T>A		intron_variant, NMD_transcript_variant		5		ENSP00000390817

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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.0615

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.375

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

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: rs1018954; hg19: chr7-21549891;