12-53328142-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001173467.3(SP7):c.*4G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,605,024 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (6 hom.)
• Consequence: SP7 NM_001173467.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.492

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 12-53328142-C-T is Benign according to our data. Variant chr12-53328142-C-T is described in ClinVar as [Benign]. Clinvar id is 284957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00554 (844/152230) while in subpopulation AFR AF= 0.0192 (797/41522). AF 95% confidence interval is 0.0181. There are 8 homozygotes in gnomad4. There are 390 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP7	NM_001173467.3	c.*4G>A		3_prime_UTR_variant	3/3	ENST00000536324.4
SP7	NM_001300837.2	c.*4G>A		3_prime_UTR_variant	3/3
SP7	NM_152860.2	c.*4G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP7	ENST00000536324.4	c.*4G>A		3_prime_UTR_variant	3/3	2	NM_001173467.3	P1
SP7	ENST00000303846.3	c.*4G>A		3_prime_UTR_variant	2/2	1		P1
SP7	ENST00000537210.2			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 842 AN: 152112 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00114 AC: 264 AN: 232556 Hom.: 1 AF XY: 0.000841 AC XY: 107 AN XY: 127286

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.000822

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000671

Gnomad OTH exome AF: 0.000176

GnomAD4 exome AF: 0.000547 AC: 795 AN: 1452794 Hom.: 6 Cov.: 29 AF XY: 0.000478 AC XY: 345 AN XY: 722180

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.000945

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000550

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.00554 AC: 844 AN: 152230 Hom.: 8 Cov.: 32 AF XY: 0.00524 AC XY: 390 AN XY: 74428

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00148 Hom.: 1

Bravo AF: 0.00643

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 25, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	13
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs115168998; hg19: chr12-53721926;