chr7-21480514-G-A

Position:

• chr7-21480514-G-A

Variant summary

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

The NM_003112.5(SP4):​c.1908-1410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,148 control chromosomes in the GnomAD database, including 43,999 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 (43999 hom., cov: 32)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP4	NM_003112.5	c.1908-1410G>A		intron_variant		ENST00000222584.8	NP_003103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP4	ENST00000222584.8	c.1908-1410G>A		intron_variant		1	NM_003112.5	ENSP00000222584	P1
SP4	ENST00000649633.1	c.1857-1410G>A		intron_variant				ENSP00000496957
SP4	ENST00000448246.1	c.*203-1410G>A		intron_variant, NMD_transcript_variant		5		ENSP00000390817

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114546 AN: 152030 Hom.: 43936 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.754 AC: 114666 AN: 152148 Hom.: 43999 Cov.: 32 AF XY: 0.756 AC XY: 56232 AN XY: 74368

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.724

Alfa AF: 0.747 Hom.: 7043

Bravo AF: 0.760

Asia WGS AF: 0.802 AC: 2785 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.82

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: rs10272006; hg19: chr7-21520132;