12-53338200-G-A

Position:

• chr12-53338200-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
SP7	NM_001300837.2	c.-271-1817C>T		intron_variant			NP_001287766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP7	ENST00000547755.1	c.-34+6914C>T		intron_variant		3		ENSP00000449355

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

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.702

Alfa AF: 0.720 Hom.: 59540

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2886129; hg19: chr12-53731984;