7-21456779-G-T

Variant names:

• chr7-21456779-G-T
• rs6461563
• NM_003112.5:c.1679-20300G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003112.5(SP4):​c.1679-20300G>T 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 152,012 control chromosomes in the GnomAD database, including 14,108 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 (14108 hom., cov: 32)
• Consequence: SP4 NM_003112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003112.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	NM_003112.5	MANE Select	c.1679-20300G>T		intron	N/A	NP_003103.2	Q02446
	SP4	NM_001326542.2		c.1628-20300G>T		intron	N/A	NP_001313471.1	A0A3B3IRW4
	SP4	NM_001326543.2		c.740-20300G>T		intron	N/A	NP_001313472.1	Q32M51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	ENST00000222584.8	TSL:1 MANE Select	c.1679-20300G>T		intron	N/A	ENSP00000222584.3	Q02446
	SP4	ENST00000959244.1		c.1670-20300G>T		intron	N/A	ENSP00000629303.1
	SP4	ENST00000649633.1		c.1628-20300G>T		intron	N/A	ENSP00000496957.1	A0A3B3IRW4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64360 AN: 151896 Hom.: 14078 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.424 AC: 64441 AN: 152012 Hom.: 14108 Cov.: 32 AF XY: 0.429 AC XY: 31905 AN XY: 74312

African (AFR) AF: 0.465 AC: 19277 AN: 41456

American (AMR) AF: 0.482 AC: 7365 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3464

East Asian (EAS) AF: 0.684 AC: 3526 AN: 5152

South Asian (SAS) AF: 0.353 AC: 1699 AN: 4814

European-Finnish (FIN) AF: 0.475 AC: 5015 AN: 10550

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25406 AN: 67978

Other (OTH) AF: 0.372 AC: 783 AN: 2104

Alfa AF: 0.360 Hom.: 5456

Bravo AF: 0.428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.22
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6461563; hg19: chr7-21496397;