12-53338107-G-A

Variant names:

• chr12-53338107-G-A
• rs10876432
• NM_001300837.2:c.-271-1724C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001300837.2(SP7):​c.-271-1724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.71 (25459 hom., cov: 20)
  • Failed GnomAD Quality Control
• Consequence: SP7 NM_001300837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 38 publications found

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]

SP7 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 12

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300837.2. 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
	SP7	NM_001300837.2		c.-271-1724C>T		intron	N/A	NP_001287766.1	Q8TDD2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP7	ENST00000547755.1	TSL:3	c.-34+7007C>T		intron	N/A	ENSP00000449355.1	F8VV67

Frequencies

GnomAD3 genomes AF: 0.707 AC: 83739 AN: 118426 Hom.: 25449 Cov.: 20

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.735

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.704

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.707 AC: 83785 AN: 118500 Hom.: 25459 Cov.: 20 AF XY: 0.716 AC XY: 41375 AN XY: 57816

African (AFR) AF: 0.639 AC: 19794 AN: 30992

American (AMR) AF: 0.763 AC: 9843 AN: 12902

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2134 AN: 2912

East Asian (EAS) AF: 0.938 AC: 4656 AN: 4962

South Asian (SAS) AF: 0.855 AC: 3650 AN: 4268

European-Finnish (FIN) AF: 0.725 AC: 5635 AN: 7774

Middle Eastern (MID) AF: 0.738 AC: 177 AN: 240

European-Non Finnish (NFE) AF: 0.696 AC: 36271 AN: 52106

Other (OTH) AF: 0.707 AC: 1188 AN: 1680

Alfa AF: 0.712 Hom.: 129981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10876432; hg19: chr12-53731891;