7-21496158-T-C

Position:

• chr7-21496158-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.2107+14035T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,940 control chromosomes in the GnomAD database, including 14,483 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 0.42 (14483 hom., cov: 32)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646

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 = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP4	NM_003112.5	c.2107+14035T>C		intron_variant		ENST00000222584.8	NP_003103.2
SP4	XM_005249829.5	c.*13534T>C		3_prime_UTR_variant	6/6		XP_005249886.1
SP4	NM_001326542.2	c.2056+14035T>C		intron_variant			NP_001313471.1
SP4	NM_001326543.2	c.1168+14035T>C		intron_variant			NP_001313472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.2107+14035T>C		intron_variant		1	NM_003112.5	ENSP00000222584	P1
SP4	ENST00000649633.1	c.2056+14035T>C		intron_variant				ENSP00000496957
SP4	ENST00000448246.1	c.*402+14035T>C		intron_variant, NMD_transcript_variant		5		ENSP00000390817

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64310 AN: 151822 Hom.: 14456 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.424 AC: 64389 AN: 151940 Hom.: 14483 Cov.: 32 AF XY: 0.431 AC XY: 32011 AN XY: 74278

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.411

Alfa AF: 0.356 Hom.: 20739

Bravo AF: 0.440

Asia WGS AF: 0.542 AC: 1882 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.78

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: rs6461569; hg19: chr7-21535776;