rs3735440

Positions:

• chr7-21511452-G-A
• chr7-21511452-G-C
• chr7-21511452-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003112.5(SP4):​c.*183G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 583,430 control chromosomes in the GnomAD database, including 153,193 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 0.75 (43750 hom., cov: 32)
  • Exomes 𝑓: 0.71 (109443 hom.)
• Consequence: SP4 NM_003112.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07

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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP4	NM_003112.5	c.*183G>A		3_prime_UTR_variant	6/6	ENST00000222584.8	NP_003103.2
SP4	NM_001326542.2	c.*183G>A		3_prime_UTR_variant	6/6		NP_001313471.1
SP4	NM_001326543.2	c.*183G>A		3_prime_UTR_variant	6/6		NP_001313472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.*183G>A		3_prime_UTR_variant	6/6	1	NM_003112.5	ENSP00000222584.3
SP4	ENST00000649633.1	c.*183G>A		3_prime_UTR_variant	6/6			ENSP00000496957.1
SP4	ENST00000448246.1	n.*833G>A		non_coding_transcript_exon_variant	5/5	5		ENSP00000390817.1
SP4	ENST00000448246.1	n.*833G>A		3_prime_UTR_variant	5/5	5		ENSP00000390817.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114302 AN: 152058 Hom.: 43687 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.708 AC: 305287 AN: 431254 Hom.: 109443 Cov.: 5 AF XY: 0.709 AC XY: 159517 AN XY: 225144

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.724

Gnomad4 ASJ exome AF: 0.711

Gnomad4 EAS exome AF: 0.912

Gnomad4 SAS exome AF: 0.736

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.752 AC: 114422 AN: 152176 Hom.: 43750 Cov.: 32 AF XY: 0.755 AC XY: 56174 AN XY: 74396

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.725

Alfa AF: 0.690 Hom.: 37555

Bravo AF: 0.758

Asia WGS AF: 0.807 AC: 2807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.70

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: rs3735440; hg19: chr7-21551070;