rs4759061

chr12-53344430-C-T

Variant summary

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

The NM_001300837.2(SP7):c.-272+258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,942 control chromosomes in the GnomAD database, including 3,788 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 0.19 (3788 hom., cov: 30)
• Consequence: SP7 NM_001300837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

Genes affected

SP7 (HGNC:17321): (Sp7 transcription factor) This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein is a bone specific transcription factor and is required for osteoblast differentiation and bone formation.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP7	NM_001300837.2	c.-272+258G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP7	ENST00000547755.1	c.-34+684G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29278 AN: 151824 Hom.: 3789 Cov.: 30

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.193 AC: 29264 AN: 151942 Hom.: 3788 Cov.: 30 AF XY: 0.189 AC XY: 14031 AN XY: 74266

Gnomad4 AFR AF: 0.0469

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0719

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.227

Alfa AF: 0.221 Hom.: 891

Bravo AF: 0.183

Asia WGS AF: 0.0520 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.3
Dann	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4759061; hg19: chr12-53738214;