chr7-21496158-T-C

Variant names:

• chr7-21496158-T-C
• rs6461569
• NM_003112.5:c.2107+14035T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	NM_003112.5	MANE Select	c.2107+14035T>C		intron	N/A	NP_003103.2
	SP4	NM_001326542.2		c.2056+14035T>C		intron	N/A	NP_001313471.1
	SP4	NM_001326543.2		c.1168+14035T>C		intron	N/A	NP_001313472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	ENST00000222584.8	TSL:1 MANE Select	c.2107+14035T>C		intron	N/A	ENSP00000222584.3
	SP4	ENST00000649633.1		c.2056+14035T>C		intron	N/A	ENSP00000496957.1
	SP4	ENST00000448246.1	TSL:5	n.*402+14035T>C		intron	N/A	ENSP00000390817.1

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

African (AFR) AF: 0.543 AC: 22487 AN: 41414

American (AMR) AF: 0.479 AC: 7306 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3466

East Asian (EAS) AF: 0.602 AC: 3107 AN: 5162

South Asian (SAS) AF: 0.549 AC: 2646 AN: 4818

European-Finnish (FIN) AF: 0.321 AC: 3396 AN: 10564

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22758 AN: 67934

Other (OTH) AF: 0.411 AC: 869 AN: 2112

Alfa AF: 0.370 Hom.: 34696

Bravo AF: 0.440

Asia WGS AF: 0.542 AC: 1882 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.78
PhyloP100		0.65
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: rs6461569; hg19: chr7-21535776;