rs2016266

Positions:

• chr12-53334171-G-A
• chr12-53334171-G-C
• chr12-53334171-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001173467.3(SP7):​c.21+1455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,004 control chromosomes in the GnomAD database, including 29,803 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 0.61 (29803 hom., cov: 31)
• Consequence: SP7 NM_001173467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP7	NM_001173467.3	c.21+1455C>T		intron_variant		ENST00000536324.4	NP_001166938.1
SP7	NM_001300837.2	c.-34+1975C>T		intron_variant			NP_001287766.1
SP7	NM_152860.2	c.21+1455C>T		intron_variant			NP_690599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP7	ENST00000536324.4	c.21+1455C>T		intron_variant		2	NM_001173467.3	ENSP00000443827	P1
SP7	ENST00000303846.3	c.21+1455C>T		intron_variant		1		ENSP00000302812	P1
SP7	ENST00000537210.2	c.-34+1975C>T		intron_variant		1		ENSP00000441367
SP7	ENST00000547755.1	c.-33-4751C>T		intron_variant		3		ENSP00000449355

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93230 AN: 151886 Hom.: 29788 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.614 AC: 93263 AN: 152004 Hom.: 29803 Cov.: 31 AF XY: 0.618 AC XY: 45932 AN XY: 74294

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.628

Alfa AF: 0.669 Hom.: 69463

Bravo AF: 0.598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.32

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: rs2016266; hg19: chr12-53727955;