rs3735440

Variant names:

• chr7-21511452-G-A
• rs3735440
• NM_003112.5:c.*183G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21511452-G-A
• chr7-21511452-G-C
• chr7-21511452-G-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.*183G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 583,430 control chromosomes in the GnomAD database, including 153,193 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 (43750 hom., cov: 32)
  • Exomes 𝑓: 0.71 (109443 hom.)
• Consequence: SP4 NM_003112.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 9 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 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.*183G>A		3_prime_UTR	Exon 6 of 6	NP_003103.2
	SP4	NM_001326542.2		c.*183G>A		3_prime_UTR	Exon 6 of 6	NP_001313471.1
	SP4	NM_001326543.2		c.*183G>A		3_prime_UTR	Exon 6 of 6	NP_001313472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP4	ENST00000222584.8	TSL:1 MANE Select	c.*183G>A		3_prime_UTR	Exon 6 of 6	ENSP00000222584.3
	SP4	ENST00000448246.1	TSL:5	n.*833G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000390817.1
	SP4	ENST00000649633.1		c.*183G>A		3_prime_UTR	Exon 6 of 6	ENSP00000496957.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114302 AN: 152058 Hom.: 43687 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.708 AC: 305287 AN: 431254 Hom.: 109443 Cov.: 5 AF XY: 0.709 AC XY: 159517 AN XY: 225144

African (AFR) AF: 0.904 AC: 11150 AN: 12340

American (AMR) AF: 0.724 AC: 11345 AN: 15662

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 9316 AN: 13108

East Asian (EAS) AF: 0.912 AC: 27530 AN: 30180

South Asian (SAS) AF: 0.736 AC: 28732 AN: 39040

European-Finnish (FIN) AF: 0.691 AC: 19283 AN: 27892

Middle Eastern (MID) AF: 0.773 AC: 1446 AN: 1870

European-Non Finnish (NFE) AF: 0.671 AC: 178777 AN: 266344

Other (OTH) AF: 0.714 AC: 17708 AN: 24818

GnomAD4 genome AF: 0.752 AC: 114422 AN: 152176 Hom.: 43750 Cov.: 32 AF XY: 0.755 AC XY: 56174 AN XY: 74396

African (AFR) AF: 0.896 AC: 37236 AN: 41558

American (AMR) AF: 0.716 AC: 10951 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2447 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4664 AN: 5180

South Asian (SAS) AF: 0.759 AC: 3666 AN: 4828

European-Finnish (FIN) AF: 0.690 AC: 7284 AN: 10556

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45811 AN: 67972

Other (OTH) AF: 0.725 AC: 1533 AN: 2114

Alfa AF: 0.702 Hom.: 106861

Bravo AF: 0.758

Asia WGS AF: 0.807 AC: 2807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		3.1
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: rs3735440; hg19: chr7-21551070;