7-21430918-A-T

Position:

• chr7-21430918-A-T

Variant summary

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

The NM_003112.5(SP4):​c.1678+75A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,144,758 control chromosomes in the GnomAD database, including 271,385 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 0.73 (41785 hom., cov: 33)
  • Exomes 𝑓: 0.68 (229600 hom.)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP4	NM_003112.5	c.1678+75A>T		intron_variant		ENST00000222584.8	NP_003103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.1678+75A>T		intron_variant		1	NM_003112.5	ENSP00000222584.3
SP4	ENST00000649633.1	c.1627+75A>T		intron_variant				ENSP00000496957.1
SP4	ENST00000432066.2	c.7+2660A>T		intron_variant		5		ENSP00000393623.2
SP4	ENST00000448246.1	n.123+2126A>T		intron_variant		5		ENSP00000390817.1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111370 AN: 152070 Hom.: 41732 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.676 AC: 670896 AN: 992570 Hom.: 229600 AF XY: 0.677 AC XY: 339882 AN XY: 501932

Gnomad4 AFR exome AF: 0.898

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.933

Gnomad4 SAS exome AF: 0.722

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.693

GnomAD4 genome AF: 0.733 AC: 111479 AN: 152188 Hom.: 41785 Cov.: 33 AF XY: 0.734 AC XY: 54625 AN XY: 74404

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.703

Alfa AF: 0.689 Hom.: 4528

Bravo AF: 0.745

Asia WGS AF: 0.806 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs40245; hg19: chr7-21470536;