12-53340722-C-T

Position:

• chr12-53340722-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+3966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,986 control chromosomes in the GnomAD database, including 10,928 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 0.36 (10928 hom., cov: 32)
• Consequence: SP7 NM_001300837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP7	NM_001300837.2	c.-272+3966G>A		intron_variant			NP_001287766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP7	ENST00000547755.1	c.-34+4392G>A		intron_variant		3		ENSP00000449355.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55106 AN: 151868 Hom.: 10913 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.363 AC: 55142 AN: 151986 Hom.: 10928 Cov.: 32 AF XY: 0.371 AC XY: 27534 AN XY: 74250

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.386

Alfa AF: 0.377 Hom.: 15040

Bravo AF: 0.361

Asia WGS AF: 0.606 AC: 2108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4759082; hg19: chr12-53734506;