chr12-53338200-G-A

Variant names:

• chr12-53338200-G-A
• rs2886129
• NM_001300837.2:c.-271-1817C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001300837.2(SP7):​c.-271-1817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,342 control chromosomes in the GnomAD database, including 37,898 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 0.70 (37898 hom., cov: 27)
• Consequence: SP7 NM_001300837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP7	NM_001300837.2	c.-271-1817C>T		intron_variant	Intron 1 of 2		NP_001287766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP7	ENST00000547755.1	c.-34+6914C>T		intron_variant	Intron 1 of 1	3		ENSP00000449355.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 105994 AN: 151224 Hom.: 37881 Cov.: 27

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.701 AC: 106057 AN: 151342 Hom.: 37898 Cov.: 27 AF XY: 0.707 AC XY: 52273 AN XY: 73890

African (AFR) AF: 0.585 AC: 24122 AN: 41216

American (AMR) AF: 0.762 AC: 11602 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2589 AN: 3466

East Asian (EAS) AF: 0.996 AC: 5100 AN: 5118

South Asian (SAS) AF: 0.925 AC: 4429 AN: 4786

European-Finnish (FIN) AF: 0.729 AC: 7607 AN: 10436

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48324 AN: 67784

Other (OTH) AF: 0.702 AC: 1480 AN: 2108

Alfa AF: 0.713 Hom.: 93134

Bravo AF: 0.695

Asia WGS AF: 0.922 AC: 3202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.88
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs2886129; hg19: chr12-53731984;