rs4759061

Variant names:

• chr12-53344430-C-T
• rs4759061
• NM_001300837.2:c.-272+258G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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.-272+258G>A		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+684G>A		intron	N/A	ENSP00000449355.1	F8VV67

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

African (AFR) AF: 0.0469 AC: 1945 AN: 41474

American (AMR) AF: 0.196 AC: 2983 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3466

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5172

South Asian (SAS) AF: 0.0719 AC: 346 AN: 4812

European-Finnish (FIN) AF: 0.272 AC: 2870 AN: 10546

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19376 AN: 67924

Other (OTH) AF: 0.227 AC: 477 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.75
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs4759061; hg19: chr12-53738214;