rs12668354

chr7-21492273-C-Achr7-21492273-C-Gchr7-21492273-C-T

Variant summary

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

The NM_003112.5(SP4):c.2107+10150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,158 control chromosomes in the GnomAD database, including 45,255 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 0.77 (45255 hom., cov: 33)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP4	NM_003112.5	c.2107+10150C>A		intron_variant		ENST00000222584.8
SP4	XM_005249829.5	c.*9649C>A		3_prime_UTR_variant	6/6
SP4	NM_001326542.2	c.2056+10150C>A		intron_variant
SP4	NM_001326543.2	c.1168+10150C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP4	ENST00000222584.8	c.2107+10150C>A		intron_variant		1	NM_003112.5	P1
SP4	ENST00000649633.1	c.2056+10150C>A		intron_variant
SP4	ENST00000448246.1	c.*402+10150C>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116466 AN: 152040 Hom.: 45195 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.766 AC: 116584 AN: 152158 Hom.: 45255 Cov.: 33 AF XY: 0.770 AC XY: 57236 AN XY: 74366

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.741

Alfa AF: 0.713 Hom.: 17318

Bravo AF: 0.771

Asia WGS AF: 0.812 AC: 2818 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.42
Dann	Benign	0.15

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: rs12668354; hg19: chr7-21531891;